Our data suggest that immunohistochemical analysis of GATA3 may be the basis for a new clinically applicable test to predict tumor recurrence early in the progression of breast cancer.
Furthermore, expression of GATA3 and MUC1 genes was analyzed by real-time RT-PCR and immunohistochemistry on breast cancer-specific tissue microarrays.
In summary, data from two independent study populations showed two intronic variants in GATA3 associated with overall decreases in breast cancer risk and suggested heterogeneity of these associations by ER status.
In univariate analysis, the presence of GATA-3 is a marker of good prognosis and predicted for superior breast cancer-specific survival, relapse-free survival, and overall survival.
The most frequently reported deregulated genes in BC include: GATA binding protein 3, arylamine N-acetyltransferase, Myb-related protein B and zinc transporter SLC39A6 precursor (overexpressed); cadherin-3 precursor, keratin type I cytoskeletal 17 and type II cytoskeletal 5 (underexpressed).
We conclude that there is no evidence that either GATA3rs570613, or any variant in strong linkage disequilibrium with it, is associated with breast cancer risk in women.
The transcription factor network composed of the oestrogen (estrogen) receptor alpha (ERalpha), FOXA1 and GATA3 may control the gene expression pattern in luminal subtype A breast cancers.
By transcriptional profiling, MBCs and the recently identified claudin-low breast cancer subset constitute related receptor-negative subgroups characterized by low expression of GATA3-regulated genes and of genes responsible for cell-cell adhesion with enrichment for markers linked to stem cell function and epithelial-to-mesenchymal transition (EMT).
This phenotype correlates with the ability of GATA3 to negatively regulate the expression of several genes that promote breast cancer lung metastasis (ID1/-3, KRTHB1, LY6E and RARRES3).
Our results highlight the role of estrogen-signaling pathways (mainly CYP19/aromatase, GATA3, and ER-beta) in the risk of locoregional recurrence of breast cancer in young women.
Analysis of publicly available databases revealed ERalpha-positive/T-bet-positive breast cancers expressing lower levels of FOXA1 (P = 0.0137) and GATA-3 (P = 0.0063) compared with ERalpha-positive/T-bet-negative breast cancers.
FOXA1, estrogen receptor alpha (ERalpha) and GATA3 independently predict favorable outcome in breast cancer patients, and their expression correlates with a differentiated, luminal tumor subtype.
Finally, in the ACI rat model of estrogen-induced breast cancer, known to be associated with elevated Aurora-A expression, we observed increased expression of GATA-3 in preinvasive and invasive mammary epithelial cells exposed to prolonged estrogen treatment and in developing breast tumors.
Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at >10% incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the luminal A subtype.
The discovery that a GATA3-miR-29b axis regulates the tumour microenvironment and inhibits metastasis opens up possibilities for therapeutic intervention in breast cancer.
Our findings demonstrate that women who carry 17-CT (OR = 0.5; p = 0.003) or 18-CT (OR = 0.41, p = 0.02) alleles of GATA3 gene are at lower risk of developing breast cancer.
Thus, approximately 20 % ER-positive breast cancers have somatic GATA3 mutations that lead to a loss of GATA3 transactivation activity and altered cell invasiveness.