GATA3

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Lua error in Module:Infobox_gene at line 33: attempt to index field 'wikibase' (a nil value). 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

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] 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.

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

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Further reading

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External links

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