GATA3

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GATA binding protein 3
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols GATA3 ; HDR; HDRS
External IDs OMIM131320 MGI95663 HomoloGene1550 GeneCards: GATA3 Gene
RNA expression pattern
PBB GE GATA3 209604 s at tn.png
PBB GE GATA3 209602 s at tn.png
PBB GE GATA3 209603 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 2625 14462
Ensembl ENSG00000107485 ENSMUSG00000015619
UniProt P23771 P23772
RefSeq (mRNA) NM_001002295 NM_008091
RefSeq (protein) NP_001002295 NP_032117
Location (UCSC) Chr 10:
8.1 – 8.12 Mb
Chr 2:
9.86 – 9.89 Mb
PubMed search [1] [2]

Trans-acting T-cell-specific transcription factor GATA-3 is a protein that in humans is encoded by the GATA3 gene.[1][2][3]

Function[edit]

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 T cell subtype while suppressing their differentiation towards Th1 cells.[5] It is hypothesised that GATA-3 may play tissue-specific roles.[6]

Clinical significance[edit]

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

In breast cancer[edit]

GATA-3 is one of the three genes mutated in >10% of breast cancers (Cancer Genome Atlas).[7]

GATA-3 was shown to be required for the luminal A type of breast cancer, intertwined in pathways with ERα[8][9] but also androgen receptor signaling in ER-/AR+ tumors.[10]

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.[11] It is highly coexpressed with FOXA1 and serves as negative predictor of basal subtype and ERBB2 subtype.[10][12][13] GATA-3 was shown to directly regulate luminal cell differentiation in mouse models of breast cancer.[14] It is also considered a strong predictor of taxane and platin salts insensitivity.

Insulin has been shown in experimental models to downregulate expression of GATA3 by causing overexpression of T-bet, resulting in resistance to endocrine therapy.[15]

Interactions[edit]

GATA3 has been shown to interact with LMO1,[16][17] ER and FOXA1.[13]

See also[edit]

References[edit]

  1. ^ Joulin V, Bories D, Eleouet JF, Labastie MC, Chretien S, Mattei MG, Romeo PH (Jul 1991). "A T-cell specific TCR delta DNA binding protein is a member of the human GATA family". EMBO J 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". J Biol Chem 279 (26): 26983–90. doi:10.1074/jbc.M403688200. PMID 15087456. 
  3. ^ "Entrez Gene: GATA3 GATA binding protein 3". 
  4. ^ Kouros-Mehr Hosein, Slorach EM, Sternlicht MD, Werb Z (December 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. ^ Int Immunol. 2011 Jul;23(7):415-20. doi: 10.1093/intimm/dxr029. Epub 2011 Jun 1. An updated view on transcription factor GATA3-mediated regulation of Th1 and Th2 cell differentiation. Yagi R, Zhu J, Paul WE.
  6. ^ Wilson BJ (2008). "Does GATA3 act in tissue-specific pathways? A meta-analysis-based approach". J. Carcinogenesis 7: 6. doi:10.4103/1477-3163.43426. PMC 2669725. PMID 19008565. 
  7. ^ Koboldt DC, Fulton RS, McLellan MD, et al. (September 2012). "Comprehensive molecular portraits of human breast tumours". Nature 490 (7418). doi:10.1038/nature11412. PMC 3465532. PMID 23000897. 
  8. ^ Wilson BJ, Giguere V (2008). "Meta-analysis of human cancer microarrays reveals that GATA3 is integral to the estrogen receptor alpha pathway". Mol Cancer 7: 49. doi:10.1186/1476-4598-7-49. PMC 2430971. PMID 18533032. 
  9. ^ 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. PMID 19483726. 
  10. ^ a b 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.  edit
  11. ^ Kouros-Mehr Hosein, Kim JW, Bechis SK, Werb Z (April 2008). "GATA-3 and the regulation of the mammary luminal cell fate". Curr. Opin. Cell Biol. 20 (2): 164–70. doi:10.1016/j.ceb.2008.02.003. PMC 2397451. PMID 18358709. 
  12. ^ 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 Res. 11 (2): R23. doi:10.1186/bcr2249. PMC 2688952. PMID 19405945. 
  13. ^ a b 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 Res. 11 (3): R40. doi:10.1186/bcr2327. PMC 2716509. PMID 19549328. 
  14. ^ Kouros-Mehr Hosein, Bechis SK, Slorach EM, Littlepage LE, Egeblad M, Ewald AJ, Pai SY, Ho IC, Werb Z (February 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. 
  15. ^ McCune K, Bhat-Nakshatri P, Thorat MA, Nephew KP, Badve S, Nakshatri H (January 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 Res. 70 (2): 685–96. doi:10.1158/0008-5472.CAN-09-1530. PMC 2807987. PMID 20068169. 
  16. ^ Ono Y, Fukuhara N, Yoshie O (December 1998). "TAL1 and LIM-only proteins synergistically induce retinaldehyde dehydrogenase 2 expression in T-cell acute lymphoblastic leukemia by acting as cofactors for GATA3". Mol. Cell. Biol. 18 (12): 6939–50. PMC 109277. PMID 9819382. 
  17. ^ Ono Y, Fukuhara N, Yoshie O (February 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". J. Biol. Chem. 272 (7): 4576–81. doi:10.1074/jbc.272.7.4576. PMID 9020185. 

Further reading[edit]

External links[edit]

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