GATA3

Trans-acting T-cell-specific transcription factor GATA-3 is a is_associated_with::protein that in humans is encoded by the GATA3 is_associated_with::gene.

Function
GATA-3 belongs to the GATA family of is_associated_with::transcription factors. It regulates luminal is_associated_with::epithelial cell differentiation in the is_associated_with::mammary gland. The protein contains two GATA-type is_associated_with::zinc fingers and is an important regulator of is_associated_with::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 is_associated_with::Th0 cells towards this T cell subtype while suppressing their differentiation towards is_associated_with::Th1 cells. It is hypothesised that GATA-3 may play tissue-specific roles.

Clinical significance
Defects in this gene are the cause of is_associated_with::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).

GATA-3 was shown to be required for the luminal A type of breast cancer, intertwined in pathways with ERα but also is_associated_with::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 is_associated_with::FOXA1 and serves as negative predictor of basal subtype and is_associated_with::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 is_associated_with::taxane and platin salts insensitivity.

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

Interactions
GATA3 has been shown to interact with is_associated_with::LMO1, ER and is_associated_with::FOXA1.