GATA3

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Identifiers
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External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
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Transcription factor GATA-3 is a protein that in humans is encoded by the GATA3 gene.[1][2][3]

Function

GATA-3 belongs to the GATA family of transcription factors. It regulates luminal epithelial cell differentiation in the mammary gland.[4] The protein contains two GATA-type zinc fingers and is an important regulator of T cell development and plays an important role in endothelial cell biology. GATA-3 has been shown to promote the secretion of IL-4, IL-5, and IL-13 from Th2 cells, and induces the differentiation of Th0 cells towards this Th2 cell subtype while suppressing their differentiation towards Th1 cells.[5] It is hypothesised that GATA-3 may play tissue-specific roles.[6] It has been suggested that GATA-3 is regulated in CD4+ T cells at a transcriptional level through the IL-4 receptor, as well as translationally through T cell receptor signaling.[7]

Clinical significance

Defects in this gene are the cause of hypoparathyroidism with sensorineural deafness and renal dysplasia.

Breast cancer

GATA-3 is one of the three genes mutated in >10% of breast cancers (Cancer Genome Atlas).[8]

GATA-3 was shown to be required for the luminal A type of breast cancer, intertwined in pathways with ERα[9][10] but also androgen receptor signaling in ER-/AR+ tumors.[11]

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.[12] It is highly coexpressed with FOXA1 and serves as negative predictor of basal subtype and ERBB2 subtype.[11][13][14] GATA-3 was shown to directly regulate luminal cell differentiation in mouse models of breast cancer.[15] It is also considered a strong predictor of taxane and platin salts insensitivity.[citation needed]

Insulin has been shown in experimental models to downregulate expression of GATA3 by causing overexpression of T-bet, resulting in resistance to endocrine therapy.[16]

Interactions

GATA3 has been shown to interact with LMO1,[17][18] ER and FOXA1.[14]

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. ↑ 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.
  5. ↑ Yagi R, Zhu J, Paul WE (Jul 2011). "An updated view on transcription factor GATA3-mediated regulation of Th1 and Th2 cell differentiation". International Immunology. 23 (7): 415–20. doi:10.1093/intimm/dxr029. PMC 3123974. PMID 21632975.
  6. ↑ Wilson BJ (2008). "Does GATA3 act in tissue-specific pathways? A meta-analysis-based approach". Journal of Carcinogenesis. 7: 6. doi:10.4103/1477-3163.43426. PMC 2669725. PMID 19008565.
  7. ↑ Cook KD, Miller J (September 15, 2010). "TCR-dependent translational control of GATA-3 enhances Th2 differentiation". Journal of Immunology. 185 (6): 3209–3216. doi:10.4049/jimmunol.0902544. PMC 3993005. PMID 20696860.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 11.0 11.1 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.
  12. ↑ Kouros-Mehr H, Kim JW, Bechis SK, Werb Z (Apr 2008). "GATA-3 and the regulation of the mammary luminal cell fate". Current Opinion in Cell Biology. 20 (2): 164–70. doi:10.1016/j.ceb.2008.02.003. PMC 2397451. PMID 18358709.
  13. ↑ Jacquemier J, Charafe-Jauffret E, Monville F, Esterni B, Extra JM, Houvenaeghel G, Xerri L, Bertucci F, Birnbaum D (2009). "Association of GATA3, P53, Ki67 status and vascular peritumoral invasion are strongly prognostic in luminal breast cancer". Breast Cancer Research. 11 (2): R23. doi:10.1186/bcr2249. PMC 2688952. PMID 19405945.
  14. ↑ 14.0 14.1 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.
  15. ↑ 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.
  16. ↑ McCune K, Bhat-Nakshatri P, Thorat MA, Nephew KP, Badve S, Nakshatri H (Jan 2010). "Prognosis of hormone-dependent breast cancers: implications of the presence of dysfunctional transcriptional networks activated by insulin via the immune transcription factor T-bet". Cancer Research. 70 (2): 685–96. doi:10.1158/0008-5472.CAN-09-1530. PMC 2807987. PMID 20068169.
  17. ↑ 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.
  18. ↑ 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.

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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