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{{Infobox_gene}}
{{Infobox_gene}}
'''Transcription factor GATA-3''' is a [[protein]] that in humans is encoded by the ''GATA3'' [[gene]].<ref name="pmid2050118">{{cite journal | vauthors = Joulin V, Bories D, Eléouet JF, Labastie MC, Chrétien S, Mattéi MG, Roméo PH | title = A T-cell specific TCR delta DNA binding protein is a member of the human GATA family | journal = The EMBO Journal | volume = 10 | issue = 7 | pages = 1809–16 | date = Jul 1991 | pmid = 2050118 | pmc = 452855 | doi =  }}</ref><ref name="pmid15087456">{{cite journal | vauthors = Yamashita M, Ukai-Tadenuma M, Miyamoto T, Sugaya K, Hosokawa H, Hasegawa A, Kimura M, Taniguchi M, DeGregori J, Nakayama T | title = Essential role of GATA3 for the maintenance of type 2 helper T (Th2) cytokine production and chromatin remodeling at the Th2 cytokine gene loci | journal = The Journal of Biological Chemistry | volume = 279 | issue = 26 | pages = 26983–90 | date = Jun 2004 | pmid = 15087456 | pmc =  | doi = 10.1074/jbc.M403688200 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: GATA3 GATA binding protein 3| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2625| accessdate = }}</ref>
'''GATA3''' is a [[transcription factor]] that in humans is encoded by the ''GATA3'' [[gene]]. Studies in animal models and humans indicate that it controls the expression of a wide range of biologically and clinically important genes.<ref name="pmid2050118">{{cite journal | vauthors = Joulin V, Bories D, Eléouet JF, Labastie MC, Chrétien S, Mattéi MG, Roméo PH | title = A T-cell specific TCR delta DNA binding protein is a member of the human GATA family | journal = The EMBO Journal | volume = 10 | issue = 7 | pages = 1809–16 | date = Jul 1991 | pmid = 2050118 | pmc = 452855 | doi =  }}</ref><ref name="pmid15087456">{{cite journal | vauthors = Yamashita M, Ukai-Tadenuma M, Miyamoto T, Sugaya K, Hosokawa H, Hasegawa A, Kimura M, Taniguchi M, DeGregori J, Nakayama T | title = Essential role of GATA3 for the maintenance of type 2 helper T (Th2) cytokine production and chromatin remodeling at the Th2 cytokine gene loci | journal = The Journal of Biological Chemistry | volume = 279 | issue = 26 | pages = 26983–90 | date = Jun 2004 | pmid = 15087456 | pmc =  | doi = 10.1074/jbc.M403688200 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: GATA3 GATA binding protein 3| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2625| accessdate = }}</ref>


== Function ==
The GATA3 transcription factor is critical for the embryonic development of various tissues as well as for [[inflammation|inflammatory]] and [[Humoral immunity|humoral]] immune responses and the proper functioning of the [[endothelium]] of [[blood vessels]]. ''GATA3'' [[haploinsufficiency]] (i.e. lose of one or the two inherited ''GATA3'' genes) results in a [[congenital]] disorder termed the [[Barakat syndrome]].<ref name="pmid29626211">{{cite journal | vauthors = Barnes PJ | title = Targeting cytokines to treat asthma and chronic obstructive pulmonary disease | journal = Nature Reviews. Immunology | volume = | issue = | pages = | date = April 2018 | pmid = 29626211 | doi = 10.1038/s41577-018-0006-6 | url = }}</ref><ref name="omim.org">{{cite web|url=http://omim.org/entry/131320|title=OMIM Entry - * 131320 - GATA-BINDING PROTEIN 3; GATA3|author=|date=|website=omim.org}}</ref><ref name="pmid27387476">{{cite journal | vauthors = Belge H, Dahan K, Cambier JF, Benoit V, Morelle J, Bloch J, Vanhille P, Pirson Y, Demoulin N | title = Clinical and mutational spectrum of hypoparathyroidism, deafness and renal dysplasia syndrome | journal = Nephrology, Dialysis, Transplantation | volume = 32 | issue = 5 | pages = 830–837 | date = May 2017 | pmid = 27387476 | doi = 10.1093/ndt/gfw271 | url = }}</ref>


GATA-3 belongs to the [[GATA transcription factor|GATA family]] of [[transcription factor]]s.  It regulates luminal [[epithelial cell]] differentiation in the [[mammary gland]].<ref name="pmid17129787">{{cite journal | vauthors = Kouros-Mehr H, Slorach EM, Sternlicht MD, Werb Z | title = GATA-3 maintains the differentiation of the luminal cell fate in the mammary gland | journal = Cell | volume = 127 | issue = 5 | pages = 1041–55 | date = Dec 2006 | pmid = 17129787 | pmc = 2646406 | doi = 10.1016/j.cell.2006.09.048 }}</ref> The protein contains two GATA-type [[zinc finger]]s and is an important regulator of [[T cell]] [[T cell development|development]] and plays an important role in [[endothelium|endothelial]] cell biology.   GATA-3 has been shown to promote the secretion of [[interleukin 4|IL-4]], [[interleukin 5|IL-5]], and [[interleukin 13|IL-13]] from [[T helper cell|Th2 cells]], and induces the differentiation of [[Th0 cell]]s towards this Th2 cell subtype while suppressing their differentiation towards [[Th1 cell]]s.<ref>{{cite journal | vauthors = Yagi R, Zhu J, Paul WE | title = An updated view on transcription factor GATA3-mediated regulation of Th1 and Th2 cell differentiation | journal = International Immunology | volume = 23 | issue = 7 | pages = 415–20 | date = Jul 2011 | pmid = 21632975 | doi = 10.1093/intimm/dxr029 | pmc=3123974}}</ref> It is hypothesised that GATA-3 may play tissue-specific roles.<ref name="pmid19008565">{{cite journal | vauthors = Wilson BJ | title = Does GATA3 act in tissue-specific pathways? A meta-analysis-based approach | journal = Journal of Carcinogenesis | volume = 7 | pages = 6 | year = 2008 | pmid = 19008565 | pmc = 2669725 | doi = 10.4103/1477-3163.43426 }}</ref> It has been suggested that GATA-3 is regulated in CD4+ T cells at a [[Transcriptional regulation|transcriptional level]] through the [[Interleukin-4 receptor|IL-4 receptor]], as well as [[Translational regulation|translationally]] through [[T cell receptor]] signaling.<ref>{{cite journal | vauthors = Cook KD, Miller J | title = TCR-dependent translational control of GATA-3 enhances Th2 differentiation | journal = Journal of Immunology | volume = 185 | issue = 6 | pages = 3209–3216 | date = September 15, 2010 | pmid = 20696860 | pmc = 3993005 | doi = 10.4049/jimmunol.0902544 }}</ref>
Current clinical and laboratory research is focusing on determining the benefits of directly or indirectly blocking the action of GATA3 in inflammatory and allergic diseases such as asthma.<ref name="pmid29626211"/> It is also proposed to be a clinically important marker for various types of cancer, particularly those of the breast. However, the role, if any, of GATA3 in the development of these cancers is under study and remains unclear.<ref name="pmid23939152">{{cite journal | vauthors = Ordóñez NG | title = Value of GATA3 immunostaining in tumor diagnosis: a review | journal = Advances in Anatomic Pathology | volume = 20 | issue = 5 | pages = 352–60 | date = September 2013 | pmid = 23939152 | doi = 10.1097/PAP.0b013e3182a28a68 | url = }}</ref>


== Clinical significance ==
== Gene ==
The ''GATA3'' gene is located close to the end of the short arm of chromosome 10 at position p14. It consists of 8 [[exons]], and codes for two variants viz., GATA3, variant 1, and GATA3, variant 2.<ref>{{cite web|url=https://www.ncbi.nlm.nih.gov/nuccore/NG_015859.1?&feature=any|title=Homo sapiens GATA binding protein 3 (GATA3), RefSeqGene on chromosome  - Nucleotide - NCBI|author=|date=|website=www.ncbi.nlm.nih.gov}}</ref> Expression of ''GATA3'' may be regulated in part or at times by the [[antisense RNA]], GATA3-AS1, whose gene is located close to the ''GATA3'' gene on the short arm of chromosome 10 at position p14.<ref>https://www.ncbi.nlm.nih.gov/gene/399717#summary</ref> Various types of [[mutations]] including [[point mutation]]s as well as small- and large-scale [[Deletion (genetics)|delitional]] mutations cause an [[autosomal dominant]] [[genetic disorder]], the Barakat syndrome (also termed hypoparathyroidism, deafness, and renal dysplasia syndrome). The location of ''GATA3'' borders that of other critical sites on chromosome 10, particularly a site located at 10p14-p13. Mutations in this site cause the congenital disorder DiGeorge syndrome/velocardiofacial syndrome complex 2 (or DiGeorge syndrome 2).<ref>{{cite web|url=https://www.ncbi.nlm.nih.gov/gtr/conditions/C1832431/|title=DiGeorge syndrome/velocardiofacial syndrome complex 2 - Conditions - GTR - NCBI|author=|date=|website=www.ncbi.nlm.nih.gov}}</ref> Large-scale deletions in ''GATA3'' may span into the DiGeorge syndrome 2 area and thereby cause a complex syndrome with features of the [[Barakat syndrome]] combined with some of those of the DiGeorge syndrome 2.<ref name="pmid27387476"/><ref name="pmid20425828">{{cite journal | vauthors = Lindstrand A, Malmgren H, Verri A, Benetti E, Eriksson M, Nordgren A, Anderlid BM, Golovleva I, Schoumans J, Blennow E | title = Molecular and clinical characterization of patients with overlapping 10p deletions | journal = American Journal of Medical Genetics. Part A | volume = 152A | issue = 5 | pages = 1233–43 | date = May 2010 | pmid = 20425828 | doi = 10.1002/ajmg.a.33366 | url = }}</ref> Knockout of both ''GATA3'' genes in mice is fatal: these animals die at embryonic days 11 and 12 due to internal bleeding. They also exhibit gross deformities in the brain and spine as well as aberrations in fetal liver hematopoiesis.<ref name="pmid26313026">{{cite journal | vauthors = Du F, Yuan P, Wang T, Zhao J, Zhao Z, Luo Y, Xu B | title = The Significance and Therapeutic Potential of GATA3 Expression and Mutation in Breast Cancer: A Systematic Review | journal = Medicinal Research Reviews | volume = 35 | issue = 6 | pages = 1300–15 | date = November 2015 | pmid = 26313026 | doi = 10.1002/med.21362 | url = }}</ref>


Defects in this gene are the cause of [[hypoparathyroidism]] with [[sensorineural hearing loss|sensorineural deafness]] and [[familial renal disease in animals|renal dysplasia]].
== Protein ==
GATA3 variant 1 is a [[Biomolecular structure#Primary structure|linear]] protein consisting of 444 [[amino acids]]. GATA3 variant 2 protein is an identically structured [[Protein isoform|isoform]] of, but 1 amino acid shorter than, GATA3 variant 1. Differences, if any, in the functions of these two variants have not been reported.<ref>{{cite web|url=https://www.ncbi.nlm.nih.gov/nuccore/NM_002051.2|title=Homo sapiens GATA binding protein 3 (GATA3), transcript variant 2, mRN - Nucleotide - NCBI|author=|date=|website=www.ncbi.nlm.nih.gov}}</ref> With respect to the best studied variant, variant 1, but presumably also variant 2, one of the [[zinc finger]] [[structural motif]]s, ZNF2, is located at the protein's [[C-terminus]] and binds to specific [[Promoter (genetics)|gene promoter]] DNA sequences to  regulate the expression of the genes controlled by these promoters. The other zinc finger, ZNF1, is at the protein's [[N-terminus]] and interacts with various nuclear factors, including [[ZFPM1|Zinc finger protein 1]] (i.e. ZFPM1, also termed Friends of GATA1 [i.e. FOG-1]) and [[ZFPM2]] (i.e. FOG-2), that modulate GATA3's gene-stimulating actions.<ref name="ncbi.nlm.nih.gov">{{cite web|url=https://www.ncbi.nlm.nih.gov/protein/50541959|title=trans-acting T-cell-specific transcription factor GATA-3 isoform 1 [Ho - Protein - NCBI|author=|date=|website=www.ncbi.nlm.nih.gov}}</ref>


=== Breast cancer ===
== Pathophysiology ==
The GATA3 transcription factor regulates the expression of genes involved in the development of various tissues as well as genes involved in [[physiological]] as well as [[pathological]] [[humoral]] inflammatory and allergic responses.<ref name="pmid27387476"/><ref name="pmid29626211"/>


GATA-3 is one of the three genes mutated in >10% of [[breast cancer]]s (Cancer Genome Atlas).<ref name="pmid23000897">{{cite journal | vauthors = Koboldt DC, Fulton RS, McLellan MD | title = Comprehensive molecular portraits of human breast tumours | journal = Nature | volume = 490 | issue = 7418 | pages = 61–70 | date = Oct 2012 | pmid = 23000897 | pmc = 3465532 | doi = 10.1038/nature11412 }}</ref>
== Function ==
GATA3 belongs to the [[GATA transcription factor|GATA family]] of [[transcription factor]]s. [[Deletion (genetics)|Gene-deletion]] studies in mice indicate that ''Gata3'' (mouse gene equivalent to GATA3) is critical for the embryonic development and/or function of various cell types (e.g. [[adipocyte|fat cells]], [[neural crest cell]]s, [[lymphocytes]]) and tissues (e.g. kidney, liver, brain, spinal cord, mammary gland).<ref name="omim.org"/> Studies in humans implicate GATA3 in the following:
*'''1)''' GATA3 is required for the development of the [[parathyroid gland]], sensory component(s) of the auditory system, and the kidney in animals and humans.<ref name="pmid27387476"/> It may also contribure to the development of the vagina and uterus in humans.<ref name="https://www.omim.org/entry/131320">https://www.omim.org/entry/131320</ref>
*'''2)''' In humans, GATA3 is required for the development and/or function of [[innate lymphoid cell]]s (ILCs), particularly [[innate lymphoid cell#Group 2 ILCs|Group 2 ILCs]] as well as for the development of [[T helper cell]]s,(Th cells), particularly [[T helper cell#Th1/Th2 model|Th2 cells]]. Group 2 ILCs and Th2 cells, and thereby GATA3, are critical for the development of allergic and [[humoral immunity|humoral immune]] responses in humans. Comparable studies in animals implicate GATA3 in the development of lymphocytes that mediate allergic and humoral immunity as well as allergic and humeral immune responses.<ref name="pmid29184556">{{cite journal | vauthors = Zhu J | title = GATA3 Regulates the Development and Functions of Innate Lymphoid Cell Subsets at Multiple Stages | journal = Frontiers in Immunology | volume = 8 | issue = | pages = 1571 | date = 2017 | pmid = 29184556 | pmc = 5694433 | doi = 10.3389/fimmu.2017.01571 | url = }}</ref><ref name="https://www.omim.org/entry/131320"/>
*'''3)''' GATA3 promotes the secretion of [[interleukin 4|IL-4]], [[interleukin 5|IL-5]], and [[interleukin 13|IL-13]] from Th2 cells in humans and has similar actions on comparable mouse lymphocytes. All three of these interleukins serve to promote allergic responses,<ref>{{cite journal | vauthors = Yagi R, Zhu J, Paul WE | title = An updated view on transcription factor GATA3-mediated regulation of Th1 and Th2 cell differentiation Z| journal = [[International Immunology]] | volume = 23 | issue = 7 | pages = 415–20 | date = Jul 2011 | pmid = 21632975 | doi = 10.1093/intimm/dxr029 | pmc=3123974}}</ref>
*'''4)''' GATA3 induces the [[Cellular differentiation|maturation]] of precursor cells into [[Breast development|breast]] [[epithelium|epithelial cells]] and maintains these cells in their mature state in mice and possibly humans.<ref name="pmid17129787">{{cite journal | vauthors = Kouros-Mehr H, Slorach EM, Sternlicht MD, Werb Z | title = GATA-3 maintains the differentiation of the luminal cell fate in the mammary gland | journal = Cell | volume = 127 | issue = 5 | pages = 1041–55 | date = Dec 2006 | pmid = 17129787 | pmc = 2646406 | doi = 10.1016/j.cell.2006.09.048 }}</ref><ref name="pmid26772397">{{cite journal | vauthors = Asch-Kendrick R, Cimino-Mathews A | title = The role of GATA3 in breast carcinomas: a review | journal = Human Pathology | volume = 48 | issue = | pages = 37–47 | date = February 2016 | pmid = 26772397 | doi = 10.1016/j.humpath.2015.09.035 | url = }}</ref>
*'''5)''' In mice, GATA3 is responsible for the normal development of various tissues including the skin, fat cells, the [[thymus]], and the nervous system.<ref name="pmid17349208">{{cite journal | vauthors = Ho IC, Pai SY | title = GATA-3 - not just for Th2 cells anymore | journal = Cellular & Molecular Immunology | volume = 4 | issue = 1 | pages = 15–29 | date = February 2007 | pmid = 17349208 | doi = | url = }}</ref><ref name="https://www.omim.org/entry/131320"/>


GATA-3 was shown to be required for the luminal A type of breast cancer, intertwined in pathways with [[estrogen receptor alpha|ERα]]<ref name="pmid18533032">{{cite journal | vauthors = Wilson BJ, Giguère V | title = Meta-analysis of human cancer microarrays reveals GATA3 is integral to the estrogen receptor alpha pathway | journal = Molecular Cancer | volume = 7 | pages = 49 | year = 2008 | pmid = 18533032 | pmc = 2430971 | doi = 10.1186/1476-4598-7-49 }}</ref><ref name="pmid19483726">{{cite journal | vauthors = Dydensborg AB, Rose AA, Wilson BJ, Grote D, Paquet M, Giguère V, Siegel PM, Bouchard M | title = GATA3 inhibits breast cancer growth and pulmonary breast cancer metastasis | journal = Oncogene | volume = 28 | issue = 29 | pages = 2634–42 | date = Jul 2009 | pmid = 19483726 | doi =  10.1038/onc.2009.126}}</ref> but also [[androgen receptor]] signaling in ER-/AR+ tumors.<ref name=Sanga_2009/>
== Clinical significance ==
=== Mutations ===
Inactivating mutations in one of the two parental GATA3 genes cause the [[congenital]] disorder of [[hypoparathyroidism]] with [[sensorineural hearing loss|sensorineural deafness]] and [[kidney disease|kidney malformations]], i.e. the [[Barakat syndrome]]. This rare syndrome may occur in families or as a new mutation in an individual from a family with no history of the disorder. Mutations in GATA3 cause variable degrees of hypoparathyroidism, deafness, and kidney disease [[birth defects]] because of '''1)''' individual differences in the [[penetrance]] of the mutation, '''2)''' a sporadic, and as yet unexplained, association with malformation of uterus and vagina, and '''3)''' mutations which extend beyond the ''GATA3'' gene into chromosomal areas where mutations are responsible for developing other types of abnormalities which are characteristics of the DeGeorge syndrome 2. The Barakat syndrome is due to a [[haploinsufficiency]] in GATA3 levels, i.e. levels of the transcription factor that are insufficient for the normal development of the cited tissues during [[embryogenesis]].<ref name="omim.org"/><ref name="pmid27387476"/><ref name="pmid20425828"/>


Nuclear expression of GATA-3 in breast cancer is considered a marker of luminal cancer in ER+ cancer and luminal androgen responsive cancer in ER-/AR+ tumors.<ref name="pmid18358709">{{cite journal | vauthors = Kouros-Mehr H, Kim JW, Bechis SK, Werb Z | title = GATA-3 and the regulation of the mammary luminal cell fate | journal = Current Opinion in Cell Biology | volume = 20 | issue = 2 | pages = 164–70 | date = Apr 2008 | pmid = 18358709 | pmc = 2397451 | doi = 10.1016/j.ceb.2008.02.003 }}</ref> It is highly coexpressed with [[FOXA1]] and serves as negative predictor of basal subtype and [[ERBB2]] subtype.<ref name=Sanga_2009>{{cite journal | vauthors = Sanga S, Broom BM, Cristini V, Edgerton ME | title = Gene expression meta-analysis supports existence of molecular apocrine breast cancer with a role for androgen receptor and implies interactions with ErbB family | journal = BMC Medical Genomics | volume = 2 | pages = 59 | year = 2009 | pmid = 19747394 | pmc = 2753593 | doi = 10.1186/1755-8794-2-59 }}</ref><ref name=Jocelyne_2009>{{cite journal | vauthors = Jacquemier J, Charafe-Jauffret E, Monville F, Esterni B, Extra JM, Houvenaeghel G, Xerri L, Bertucci F, Birnbaum D | title = Association of GATA3, P53, Ki67 status and vascular peritumoral invasion are strongly prognostic in luminal breast cancer | journal = Breast Cancer Research | volume = 11 | issue = 2 | pages = R23 | year = 2009 | pmid = 19405945 | pmc = 2688952 | doi = 10.1186/bcr2249 }}</ref><ref name=Albergaria_2009 >{{cite journal | vauthors = Albergaria A, Paredes J, Sousa B, Milanezi F, Carneiro V, Bastos J, Costa S, Vieira D, Lopes N, Lam EW, Lunet N, Schmitt F | title = Expression of FOXA1 and GATA-3 in breast cancer: the prognostic significance in hormone receptor-negative tumours | journal = Breast Cancer Research | volume = 11 | issue = 3 | pages = R40 | year = 2009 | pmid = 19549328 | pmc = 2716509 | doi = 10.1186/bcr2327 }}</ref> GATA-3 was shown to directly regulate luminal cell differentiation in mouse models of breast cancer.<ref name="pmid18242514">{{cite journal | vauthors = Kouros-Mehr H, Bechis SK, Slorach EM, Littlepage LE, Egeblad M, Ewald AJ, Pai SY, Ho IC, Werb Z | title = GATA-3 links tumor differentiation and dissemination in a luminal breast cancer model | journal = Cancer Cell | volume = 13 | issue = 2 | pages = 141–52 | date = Feb 2008 | pmid = 18242514 | pmc = 2262951 | doi = 10.1016/j.ccr.2008.01.011 }}</ref> It is also considered a strong predictor of [[taxane]] and [[Alkylating antineoplastic agent#Alkylating-like|platin salt]]s insensitivity.{{citation needed|date=August 2016}}
=== Allergy ===
Mouse studies indicate that inhibiting the expression of GATA3 using [[antisense RNA]] methods suppresses allergic inflammation. The protein is overexpressed in the afflicted tissues of individuals with various forms of allergy including asthma, rhinitis, nasal polyps, and atopic eczema. This suggests that it may have a role in promoting these disorders.<ref name="pmid26654192">{{cite journal | vauthors = Bachert C, Zhang L, Gevaert P | title = Current and future treatment options for adult chronic rhinosinusitis: Focus on nasal polyposis | journal = The Journal of Allergy and Clinical Immunology | volume = 136 | issue = 6 | pages = 1431–1440 | date = December 2015 | pmid = 26654192 | doi = 10.1016/j.jaci.2015.10.010 | url = }}</ref> In a [[Phases of clinical research#Phase II|phase IIA clinical study]] of individuals suffering allergen-induced asthma, inhalation of [[Deoxyribozyme]] ST010, which specifically inactivates GATA3 [[messenger RNA]], for 28 days reduced early and late immune lung responses to inhaled allergen. The clinical benefit of inhibiting GATA3 in this disorder is thought to be due to interfering with the function of Group 2 ILCs and Th2 cells by, for example, reducing there production of IL-4, IL-13, and especially IL-5. Reduction in these [[eosinophil]]-stimulating interleukins, it is postulated, reduces this cells ability to promote allergic reactivity and responses.<ref name="pmid29626211"/><ref name="pmid27910098">{{cite journal | vauthors = Garn H, Renz H | title = GATA-3-specific DNAzyme - A novel approach for stratified asthma therapy | journal = European Journal of Immunology | volume = 47 | issue = 1 | pages = 22–30 | date = January 2017 | pmid = 27910098 | doi = 10.1002/eji.201646450 | url = }}</ref> For similar reasons, this treatment might also prove to be clinical useful for treating other allergic disorders.<ref name="pmid26654192"/>


[[Insulin]] has been shown in experimental models to downregulate expression of GATA3 by causing overexpression of [[T-bet]], resulting in resistance to endocrine therapy.<ref name=McClune_2010>{{cite journal | vauthors = McCune K, Bhat-Nakshatri P, Thorat MA, Nephew KP, Badve S, Nakshatri H | title = Prognosis of hormone-dependent breast cancers: implications of the presence of dysfunctional transcriptional networks activated by insulin via the immune transcription factor T-bet | journal = Cancer Research | volume = 70 | issue = 2 | pages = 685–96 | date = Jan 2010 | pmid = 20068169 | pmc = 2807987 | doi = 10.1158/0008-5472.CAN-09-1530 }}</ref>
=== Tumors ===
==== Breast tumors ====
===== Development =====
''GATA3'' is one of the three genes mutated in >10% of [[breast cancer]]s (Cancer Genome Atlas).<ref name="pmid23000897">{{cite journal | vauthors = Koboldt DC, Fulton RS, McLellan MD | title = Comprehensive molecular portraits of human breast tumours | journal = Nature | volume = 490 | issue = 7418 | pages = 61–70 | date = Oct 2012 | pmid = 23000897 | pmc = 3465532 | doi = 10.1038/nature11412 }}</ref> Studies in mice indicate that the gene is critical for the normal development of breast tissue and directly regulates luminal cell (i.e. cells lining mammary ducts) differentiation in experimentally induced breast cancer.<ref name="pmid26313026"/><ref name="pmid18242514">{{cite journal | vauthors = Kouros-Mehr H, Bechis SK, Slorach EM, Littlepage LE, Egeblad M, Ewald AJ, Pai SY, Ho IC, Werb Z | title = GATA-3 links tumor differentiation and dissemination in a luminal breast cancer model | journal = Cancer Cell | volume = 13 | issue = 2 | pages = 141–52 | date = Feb 2008 | pmid = 18242514 | pmc = 2262951 | doi = 10.1016/j.ccr.2008.01.011 }}</ref>  Analytic studies of human breast cancer tissues suggest that ''GATA3'' is required for specific type of low risk breast cancer (i.e. luminal A), is integral to the expression of [[estrogen receptor alpha]], and (in estrogen receptor negative/androgen receptor positive cancers) [[androgen receptor]] signaling.<ref name="pmid18533032">{{cite journal | vauthors = Wilson BJ, Giguère V | title = Meta-analysis of human cancer microarrays reveals GATA3 is integral to the estrogen receptor alpha pathway | journal = Molecular Cancer | volume = 7 | pages = 49 | year = 2008 | pmid = 18533032 | pmc = 2430971 | doi = 10.1186/1476-4598-7-49 }}</ref><ref name="pmid19483726">{{cite journal | vauthors = Dydensborg AB, Rose AA, Wilson BJ, Grote D, Paquet M, Giguère V, Siegel PM, Bouchard M | title = GATA3 inhibits breast cancer growth and pulmonary breast cancer metastasis | journal = Oncogene | volume = 28 | issue = 29 | pages = 2634–42 | date = Jul 2009 | pmid = 19483726 | doi =  10.1038/onc.2009.126}}</ref><ref name=Sanga_2009>{{cite journal | vauthors = Sanga S, Broom BM, Cristini V, Edgerton ME | title = Gene expression meta-analysis supports existence of molecular apocrine breast cancer with a role for androgen receptor and implies interactions with ErbB family | journal = BMC Medical Genomics | volume = 2 | pages = 59 | year = 2009 | pmid = 19747394 | pmc = 2753593 | doi = 10.1186/1755-8794-2-59 }}</ref> These studies suggest that ''GATA3'' is involved in the development of at least certain types of breast cancer in humans. However, there is disagreement on this, with some studies suggesting that the expression of the ''GATA3'' acts to inhibit and other studies suggesting that it acts to promote the development, growth, and/or spread of this cancer. Further studies are needed to elucidate the role, if any, of GATA3 in the development of breast cancer.<ref name="pmid26313026"/>
 
===== Marker =====
[[Immunocytochemistry|Immuocytochemical]] analysis of GATA3 protein in breast cells is a valuable marker for diagnosing primary breast cancer, being tested as positive in up to 94% of cases. It is especially valuable for estrogen receptor positive breast cancers but is less sensitive (435-66% elevated), although still more valuable than many other markers, for diagnosing [[triple-negative breast cancer]]s. This analysis is widely used as a clinically valuable marker for breast cancer.<ref name="pmid22706858">{{cite journal | vauthors = Liu H, Shi J, Wilkerson ML, Lin F | title = Immunohistochemical evaluation of GATA3 expression in tumors and normal tissues: a useful immunomarker for breast and urothelial carcinomas | journal = American Journal of Clinical Pathology | volume = 138 | issue = 1 | pages = 57–64 | date = July 2012 | pmid = 22706858 | doi = 10.1309/AJCP5UAFMSA9ZQBZ | url = }}</ref><ref name="pmid28574279">{{cite journal | vauthors = Peng Y, Butt YM, Chen B, Zhang X, Tang P | title = Update on Immunohistochemical Analysis in Breast Lesions | journal = Archives of Pathology & Laboratory Medicine | volume = 141 | issue = 8 | pages = 1033–1051 | date = August 2017 | pmid = 28574279 | doi = 10.5858/arpa.2016-0482-RA | url = }}</ref>
 
==== Other tumor types ====
Similar to breast tumors, the role of ''GATA3'' in the genesis of other tumor types is unclear but detection of its transcription factor product may be diagnostically useful. Immuocytochemical analysis of GATA3 protein is considered a valuable marker for certain types of [[Bladder cancer|urinary bladder]] and [[urethral cancer]]s as well as for [[parathyroid gland]] tumors (cancerous or benign), Single series reports suggest that this analysis might also be of value for diagnosing [[salivary gland tumor]]s, [[salivary duct carcinoma]]s, [[mammary analog secretory carcinoma]]s, benign ovarian [[Brenner tumor]]s, benign  [[Walthard cell rest]]s, and [[paraganglioma]]s.<ref name="pmid29614760">{{cite journal | vauthors = Inamura K | title = Bladder Cancer: New Insights into Its Molecular Pathology | journal = Cancers | volume = 10 | issue = 4 | pages = | date = April 2018 | pmid = 29614760 | doi = 10.3390/cancers10040100 | url = }}</ref><ref name="pmid23939152"/>


== Interactions ==
== Interactions ==
 
GATA3 has been shown to [[Protein-protein interaction|interact]] with the following transcription factor regulators: [[ZFPM1]] and [[ZFPM2]];<ref name="ncbi.nlm.nih.gov"/> [[LMO1]];<ref name="pmid9819382">{{cite journal | vauthors = Ono Y, Fukuhara N, Yoshie O | title = TAL1 and LIM-only proteins synergistically induce retinaldehyde dehydrogenase 2 expression in T-cell acute lymphoblastic leukemia by acting as cofactors for GATA3 | journal = Molecular and Cellular Biology | volume = 18 | issue = 12 | pages = 6939–50 | date = Dec 1998 | pmid = 9819382 | pmc = 109277 | doi =  }}</ref><ref name="pmid9020185">{{cite journal | vauthors = Ono Y, Fukuhara N, Yoshie O | title = Transcriptional activity of TAL1 in T cell acute lymphoblastic leukemia (T-ALL) requires RBTN1 or -2 and induces TALLA1, a highly specific tumor marker of T-ALL | journal = The Journal of Biological Chemistry | volume = 272 | issue = 7 | pages = 4576–81 | date = Feb 1997 | pmid = 9020185 | doi = 10.1074/jbc.272.7.4576 }}</ref> and [[FOXA1]].<ref name=Albergaria_2009 >{{cite journal | vauthors = Albergaria A, Paredes J, Sousa B, Milanezi F, Carneiro V, Bastos J, Costa S, Vieira D, Lopes N, Lam EW, Lunet N, Schmitt F | title = Expression of FOXA1 and GATA-3 in breast cancer: the prognostic significance in hormone receptor-negative tumours | journal = Breast Cancer Research | volume = 11 | issue = 3 | pages = R40 | year = 2009 | pmid = 19549328 | pmc = 2716509 | doi = 10.1186/bcr2327 }}</ref> These regulators may promote or inhibit GATA3 in stimulating the expression of its target genes.
GATA3 has been shown to [[Protein-protein interaction|interact]] with [[LMO1]],<ref name="pmid9819382">{{cite journal | vauthors = Ono Y, Fukuhara N, Yoshie O | title = TAL1 and LIM-only proteins synergistically induce retinaldehyde dehydrogenase 2 expression in T-cell acute lymphoblastic leukemia by acting as cofactors for GATA3 | journal = Molecular and Cellular Biology | volume = 18 | issue = 12 | pages = 6939–50 | date = Dec 1998 | pmid = 9819382 | pmc = 109277 | doi =  }}</ref><ref name="pmid9020185">{{cite journal | vauthors = Ono Y, Fukuhara N, Yoshie O | title = Transcriptional activity of TAL1 in T cell acute lymphoblastic leukemia (T-ALL) requires RBTN1 or -2 and induces TALLA1, a highly specific tumor marker of T-ALL | journal = The Journal of Biological Chemistry | volume = 272 | issue = 7 | pages = 4576–81 | date = Feb 1997 | pmid = 9020185 | doi = 10.1074/jbc.272.7.4576 }}</ref> ER and [[FOXA1]].<ref name="Albergaria_2009"/>


== See also ==
== See also ==
* [[GATA transcription factor]]
* [[GATA transcription factor]]s
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Latest revision as of 00:24, 8 December 2018

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Identifiers
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External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
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GATA3 is a transcription factor that in humans is encoded by the GATA3 gene. Studies in animal models and humans indicate that it controls the expression of a wide range of biologically and clinically important genes.[1][2][3]

The GATA3 transcription factor is critical for the embryonic development of various tissues as well as for inflammatory and humoral immune responses and the proper functioning of the endothelium of blood vessels. GATA3 haploinsufficiency (i.e. lose of one or the two inherited GATA3 genes) results in a congenital disorder termed the Barakat syndrome.[4][5][6]

Current clinical and laboratory research is focusing on determining the benefits of directly or indirectly blocking the action of GATA3 in inflammatory and allergic diseases such as asthma.[4] It is also proposed to be a clinically important marker for various types of cancer, particularly those of the breast. However, the role, if any, of GATA3 in the development of these cancers is under study and remains unclear.[7]

Gene

The GATA3 gene is located close to the end of the short arm of chromosome 10 at position p14. It consists of 8 exons, and codes for two variants viz., GATA3, variant 1, and GATA3, variant 2.[8] Expression of GATA3 may be regulated in part or at times by the antisense RNA, GATA3-AS1, whose gene is located close to the GATA3 gene on the short arm of chromosome 10 at position p14.[9] Various types of mutations including point mutations as well as small- and large-scale delitional mutations cause an autosomal dominant genetic disorder, the Barakat syndrome (also termed hypoparathyroidism, deafness, and renal dysplasia syndrome). The location of GATA3 borders that of other critical sites on chromosome 10, particularly a site located at 10p14-p13. Mutations in this site cause the congenital disorder DiGeorge syndrome/velocardiofacial syndrome complex 2 (or DiGeorge syndrome 2).[10] Large-scale deletions in GATA3 may span into the DiGeorge syndrome 2 area and thereby cause a complex syndrome with features of the Barakat syndrome combined with some of those of the DiGeorge syndrome 2.[6][11] Knockout of both GATA3 genes in mice is fatal: these animals die at embryonic days 11 and 12 due to internal bleeding. They also exhibit gross deformities in the brain and spine as well as aberrations in fetal liver hematopoiesis.[12]

Protein

GATA3 variant 1 is a linear protein consisting of 444 amino acids. GATA3 variant 2 protein is an identically structured isoform of, but 1 amino acid shorter than, GATA3 variant 1. Differences, if any, in the functions of these two variants have not been reported.[13] With respect to the best studied variant, variant 1, but presumably also variant 2, one of the zinc finger structural motifs, ZNF2, is located at the protein's C-terminus and binds to specific gene promoter DNA sequences to regulate the expression of the genes controlled by these promoters. The other zinc finger, ZNF1, is at the protein's N-terminus and interacts with various nuclear factors, including Zinc finger protein 1 (i.e. ZFPM1, also termed Friends of GATA1 [i.e. FOG-1]) and ZFPM2 (i.e. FOG-2), that modulate GATA3's gene-stimulating actions.[14]

Pathophysiology

The GATA3 transcription factor regulates the expression of genes involved in the development of various tissues as well as genes involved in physiological as well as pathological humoral inflammatory and allergic responses.[6][4]

Function

GATA3 belongs to the GATA family of transcription factors. Gene-deletion studies in mice indicate that Gata3 (mouse gene equivalent to GATA3) is critical for the embryonic development and/or function of various cell types (e.g. fat cells, neural crest cells, lymphocytes) and tissues (e.g. kidney, liver, brain, spinal cord, mammary gland).[5] Studies in humans implicate GATA3 in the following:

  • 1) GATA3 is required for the development of the parathyroid gland, sensory component(s) of the auditory system, and the kidney in animals and humans.[6] It may also contribure to the development of the vagina and uterus in humans.[15]
  • 2) In humans, GATA3 is required for the development and/or function of innate lymphoid cells (ILCs), particularly Group 2 ILCs as well as for the development of T helper cells,(Th cells), particularly Th2 cells. Group 2 ILCs and Th2 cells, and thereby GATA3, are critical for the development of allergic and humoral immune responses in humans. Comparable studies in animals implicate GATA3 in the development of lymphocytes that mediate allergic and humoral immunity as well as allergic and humeral immune responses.[16][15]
  • 3) GATA3 promotes the secretion of IL-4, IL-5, and IL-13 from Th2 cells in humans and has similar actions on comparable mouse lymphocytes. All three of these interleukins serve to promote allergic responses,[17]
  • 4) GATA3 induces the maturation of precursor cells into breast epithelial cells and maintains these cells in their mature state in mice and possibly humans.[18][19]
  • 5) In mice, GATA3 is responsible for the normal development of various tissues including the skin, fat cells, the thymus, and the nervous system.[20][15]

Clinical significance

Mutations

Inactivating mutations in one of the two parental GATA3 genes cause the congenital disorder of hypoparathyroidism with sensorineural deafness and kidney malformations, i.e. the Barakat syndrome. This rare syndrome may occur in families or as a new mutation in an individual from a family with no history of the disorder. Mutations in GATA3 cause variable degrees of hypoparathyroidism, deafness, and kidney disease birth defects because of 1) individual differences in the penetrance of the mutation, 2) a sporadic, and as yet unexplained, association with malformation of uterus and vagina, and 3) mutations which extend beyond the GATA3 gene into chromosomal areas where mutations are responsible for developing other types of abnormalities which are characteristics of the DeGeorge syndrome 2. The Barakat syndrome is due to a haploinsufficiency in GATA3 levels, i.e. levels of the transcription factor that are insufficient for the normal development of the cited tissues during embryogenesis.[5][6][11]

Allergy

Mouse studies indicate that inhibiting the expression of GATA3 using antisense RNA methods suppresses allergic inflammation. The protein is overexpressed in the afflicted tissues of individuals with various forms of allergy including asthma, rhinitis, nasal polyps, and atopic eczema. This suggests that it may have a role in promoting these disorders.[21] In a phase IIA clinical study of individuals suffering allergen-induced asthma, inhalation of Deoxyribozyme ST010, which specifically inactivates GATA3 messenger RNA, for 28 days reduced early and late immune lung responses to inhaled allergen. The clinical benefit of inhibiting GATA3 in this disorder is thought to be due to interfering with the function of Group 2 ILCs and Th2 cells by, for example, reducing there production of IL-4, IL-13, and especially IL-5. Reduction in these eosinophil-stimulating interleukins, it is postulated, reduces this cells ability to promote allergic reactivity and responses.[4][22] For similar reasons, this treatment might also prove to be clinical useful for treating other allergic disorders.[21]

Tumors

Breast tumors

Development

GATA3 is one of the three genes mutated in >10% of breast cancers (Cancer Genome Atlas).[23] Studies in mice indicate that the gene is critical for the normal development of breast tissue and directly regulates luminal cell (i.e. cells lining mammary ducts) differentiation in experimentally induced breast cancer.[12][24] Analytic studies of human breast cancer tissues suggest that GATA3 is required for specific type of low risk breast cancer (i.e. luminal A), is integral to the expression of estrogen receptor alpha, and (in estrogen receptor negative/androgen receptor positive cancers) androgen receptor signaling.[25][26][27] These studies suggest that GATA3 is involved in the development of at least certain types of breast cancer in humans. However, there is disagreement on this, with some studies suggesting that the expression of the GATA3 acts to inhibit and other studies suggesting that it acts to promote the development, growth, and/or spread of this cancer. Further studies are needed to elucidate the role, if any, of GATA3 in the development of breast cancer.[12]

Marker

Immuocytochemical analysis of GATA3 protein in breast cells is a valuable marker for diagnosing primary breast cancer, being tested as positive in up to 94% of cases. It is especially valuable for estrogen receptor positive breast cancers but is less sensitive (435-66% elevated), although still more valuable than many other markers, for diagnosing triple-negative breast cancers. This analysis is widely used as a clinically valuable marker for breast cancer.[28][29]

Other tumor types

Similar to breast tumors, the role of GATA3 in the genesis of other tumor types is unclear but detection of its transcription factor product may be diagnostically useful. Immuocytochemical analysis of GATA3 protein is considered a valuable marker for certain types of urinary bladder and urethral cancers as well as for parathyroid gland tumors (cancerous or benign), Single series reports suggest that this analysis might also be of value for diagnosing salivary gland tumors, salivary duct carcinomas, mammary analog secretory carcinomas, benign ovarian Brenner tumors, benign Walthard cell rests, and paragangliomas.[30][7]

Interactions

GATA3 has been shown to interact with the following transcription factor regulators: ZFPM1 and ZFPM2;[14] LMO1;[31][32] and FOXA1.[33] These regulators may promote or inhibit GATA3 in stimulating the expression of its target genes.

See also

References

  1. ↑ Joulin V, Bories D, Eléouet JF, Labastie MC, Chrétien S, Mattéi MG, Roméo PH (Jul 1991). "A T-cell specific TCR delta DNA binding protein is a member of the human GATA family". The EMBO Journal. 10 (7): 1809–16. PMC 452855. PMID 2050118.
  2. ↑ Yamashita M, Ukai-Tadenuma M, Miyamoto T, Sugaya K, Hosokawa H, Hasegawa A, Kimura M, Taniguchi M, DeGregori J, Nakayama T (Jun 2004). "Essential role of GATA3 for the maintenance of type 2 helper T (Th2) cytokine production and chromatin remodeling at the Th2 cytokine gene loci". The Journal of Biological Chemistry. 279 (26): 26983–90. doi:10.1074/jbc.M403688200. PMID 15087456.
  3. ↑ "Entrez Gene: GATA3 GATA binding protein 3".
  4. ↑ 4.0 4.1 4.2 4.3 Barnes PJ (April 2018). "Targeting cytokines to treat asthma and chronic obstructive pulmonary disease". Nature Reviews. Immunology. doi:10.1038/s41577-018-0006-6. PMID 29626211.
  5. ↑ 5.0 5.1 5.2 "OMIM Entry - * 131320 - GATA-BINDING PROTEIN 3; GATA3". omim.org.
  6. ↑ 6.0 6.1 6.2 6.3 6.4 Belge H, Dahan K, Cambier JF, Benoit V, Morelle J, Bloch J, Vanhille P, Pirson Y, Demoulin N (May 2017). "Clinical and mutational spectrum of hypoparathyroidism, deafness and renal dysplasia syndrome". Nephrology, Dialysis, Transplantation. 32 (5): 830–837. doi:10.1093/ndt/gfw271. PMID 27387476.
  7. ↑ 7.0 7.1 Ordóñez NG (September 2013). "Value of GATA3 immunostaining in tumor diagnosis: a review". Advances in Anatomic Pathology. 20 (5): 352–60. doi:10.1097/PAP.0b013e3182a28a68. PMID 23939152.
  8. ↑ "Homo sapiens GATA binding protein 3 (GATA3), RefSeqGene on chromosome - Nucleotide - NCBI". www.ncbi.nlm.nih.gov.
  9. ↑ https://www.ncbi.nlm.nih.gov/gene/399717#summary
  10. ↑ "DiGeorge syndrome/velocardiofacial syndrome complex 2 - Conditions - GTR - NCBI". www.ncbi.nlm.nih.gov.
  11. ↑ 11.0 11.1 Lindstrand A, Malmgren H, Verri A, Benetti E, Eriksson M, Nordgren A, Anderlid BM, Golovleva I, Schoumans J, Blennow E (May 2010). "Molecular and clinical characterization of patients with overlapping 10p deletions". American Journal of Medical Genetics. Part A. 152A (5): 1233–43. doi:10.1002/ajmg.a.33366. PMID 20425828.
  12. ↑ 12.0 12.1 12.2 Du F, Yuan P, Wang T, Zhao J, Zhao Z, Luo Y, Xu B (November 2015). "The Significance and Therapeutic Potential of GATA3 Expression and Mutation in Breast Cancer: A Systematic Review". Medicinal Research Reviews. 35 (6): 1300–15. doi:10.1002/med.21362. PMID 26313026.
  13. ↑ "Homo sapiens GATA binding protein 3 (GATA3), transcript variant 2, mRN - Nucleotide - NCBI". www.ncbi.nlm.nih.gov.
  14. ↑ 14.0 14.1 "trans-acting T-cell-specific transcription factor GATA-3 isoform 1 [Ho - Protein - NCBI". www.ncbi.nlm.nih.gov.
  15. ↑ 15.0 15.1 15.2 https://www.omim.org/entry/131320
  16. ↑ Zhu J (2017). "GATA3 Regulates the Development and Functions of Innate Lymphoid Cell Subsets at Multiple Stages". Frontiers in Immunology. 8: 1571. doi:10.3389/fimmu.2017.01571. PMC 5694433. PMID 29184556.
  17. ↑ Yagi R, Zhu J, Paul WE (Jul 2011). "An updated view on transcription factor GATA3-mediated regulation of Th1 and Th2 cell differentiation Z". International Immunology. 23 (7): 415–20. doi:10.1093/intimm/dxr029. PMC 3123974. PMID 21632975.
  18. ↑ Kouros-Mehr H, Slorach EM, Sternlicht MD, Werb Z (Dec 2006). "GATA-3 maintains the differentiation of the luminal cell fate in the mammary gland". Cell. 127 (5): 1041–55. doi:10.1016/j.cell.2006.09.048. PMC 2646406. PMID 17129787.
  19. ↑ Asch-Kendrick R, Cimino-Mathews A (February 2016). "The role of GATA3 in breast carcinomas: a review". Human Pathology. 48: 37–47. doi:10.1016/j.humpath.2015.09.035. PMID 26772397.
  20. ↑ Ho IC, Pai SY (February 2007). "GATA-3 - not just for Th2 cells anymore". Cellular & Molecular Immunology. 4 (1): 15–29. PMID 17349208.
  21. ↑ 21.0 21.1 Bachert C, Zhang L, Gevaert P (December 2015). "Current and future treatment options for adult chronic rhinosinusitis: Focus on nasal polyposis". The Journal of Allergy and Clinical Immunology. 136 (6): 1431–1440. doi:10.1016/j.jaci.2015.10.010. PMID 26654192.
  22. ↑ Garn H, Renz H (January 2017). "GATA-3-specific DNAzyme - A novel approach for stratified asthma therapy". European Journal of Immunology. 47 (1): 22–30. doi:10.1002/eji.201646450. PMID 27910098.
  23. ↑ Koboldt DC, Fulton RS, McLellan MD (Oct 2012). "Comprehensive molecular portraits of human breast tumours". Nature. 490 (7418): 61–70. doi:10.1038/nature11412. PMC 3465532. PMID 23000897.
  24. ↑ Kouros-Mehr H, Bechis SK, Slorach EM, Littlepage LE, Egeblad M, Ewald AJ, Pai SY, Ho IC, Werb Z (Feb 2008). "GATA-3 links tumor differentiation and dissemination in a luminal breast cancer model". Cancer Cell. 13 (2): 141–52. doi:10.1016/j.ccr.2008.01.011. PMC 2262951. PMID 18242514.
  25. ↑ Wilson BJ, Giguère V (2008). "Meta-analysis of human cancer microarrays reveals GATA3 is integral to the estrogen receptor alpha pathway". Molecular Cancer. 7: 49. doi:10.1186/1476-4598-7-49. PMC 2430971. PMID 18533032.
  26. ↑ Dydensborg AB, Rose AA, Wilson BJ, Grote D, Paquet M, Giguère V, Siegel PM, Bouchard M (Jul 2009). "GATA3 inhibits breast cancer growth and pulmonary breast cancer metastasis". Oncogene. 28 (29): 2634–42. doi:10.1038/onc.2009.126. PMID 19483726.
  27. ↑ Sanga S, Broom BM, Cristini V, Edgerton ME (2009). "Gene expression meta-analysis supports existence of molecular apocrine breast cancer with a role for androgen receptor and implies interactions with ErbB family". BMC Medical Genomics. 2: 59. doi:10.1186/1755-8794-2-59. PMC 2753593. PMID 19747394.
  28. ↑ Liu H, Shi J, Wilkerson ML, Lin F (July 2012). "Immunohistochemical evaluation of GATA3 expression in tumors and normal tissues: a useful immunomarker for breast and urothelial carcinomas". American Journal of Clinical Pathology. 138 (1): 57–64. doi:10.1309/AJCP5UAFMSA9ZQBZ. PMID 22706858.
  29. ↑ Peng Y, Butt YM, Chen B, Zhang X, Tang P (August 2017). "Update on Immunohistochemical Analysis in Breast Lesions". Archives of Pathology & Laboratory Medicine. 141 (8): 1033–1051. doi:10.5858/arpa.2016-0482-RA. PMID 28574279.
  30. ↑ Inamura K (April 2018). "Bladder Cancer: New Insights into Its Molecular Pathology". Cancers. 10 (4). doi:10.3390/cancers10040100. PMID 29614760.
  31. ↑ Ono Y, Fukuhara N, Yoshie O (Dec 1998). "TAL1 and LIM-only proteins synergistically induce retinaldehyde dehydrogenase 2 expression in T-cell acute lymphoblastic leukemia by acting as cofactors for GATA3". Molecular and Cellular Biology. 18 (12): 6939–50. PMC 109277. PMID 9819382.
  32. ↑ Ono Y, Fukuhara N, Yoshie O (Feb 1997). "Transcriptional activity of TAL1 in T cell acute lymphoblastic leukemia (T-ALL) requires RBTN1 or -2 and induces TALLA1, a highly specific tumor marker of T-ALL". The Journal of Biological Chemistry. 272 (7): 4576–81. doi:10.1074/jbc.272.7.4576. PMID 9020185.
  33. ↑ Albergaria A, Paredes J, Sousa B, Milanezi F, Carneiro V, Bastos J, Costa S, Vieira D, Lopes N, Lam EW, Lunet N, Schmitt F (2009). "Expression of FOXA1 and GATA-3 in breast cancer: the prognostic significance in hormone receptor-negative tumours". Breast Cancer Research. 11 (3): R40. doi:10.1186/bcr2327. PMC 2716509. PMID 19549328.

Further reading

External links

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