GATA-3 belongs to the GATA family of transcription factors. GATA-3 regulates luminal epithelial cell differentiation in the mammary gland. 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. It is hypothesised that GATA-3 may play tissue-specific roles.
GATA-3 is one of the three genes mutated in >10% of breast cancers (Cancer Genome Atlas).
GATA-3 was shown to be required for the luminal A type of breast cancer, intertwined in pathways with ERα but also androgen receptor signaling in ER-/AR+ tumors.
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. It is highly coexpressed with FOXA1 and serves as negative predictor of basal subtype and ERBB2 subtype. GATA-3 was shown to directly regulate luminal cell differentiation in mouse models of breast cancer. 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.
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