The FOXA family of
transcription factors regulates
chromatin structure and gene expression especially during embryonic development. In normal breast tissue FOXA1 acts throughout mammary development; whereas in
breast carcinoma its expression promotes
luminal phenotype and correlates with good prognosis. However, the role of FOXA2 has not been previously studied in
breast cancer. Our purpose was to analyze the expression of FOXA2 in
breast cancer cells, to explore its role in
breast cancer stem cells, and to correlate its
mRNA expression with clinicopathological features and outcome in a series of patients diagnosed with
breast carcinoma. We analyzed FOXA2
mRNA expression in a retrospective cohort of 230
breast cancer patients and in cell lines. We also knocked down FOXA2
mRNA expression by
siRNA to determine the impact on cell proliferation and mammospheres formation using a cancer stem cells culture assay. In vitro studies demonstrated higher FOXA2
mRNA expression in Triple-Negative/Basal-like cells. Further, when it was knocked down, cells decreased proliferation and its capability of forming mammospheres. Similarly, FOXA2
mRNA expression was detected in 10% (23/230) of the
tumors, especially in Triple-Negative/Basal-like phenotype (p < 0.001, Fisher's test). Patients whose
tumors expressed FOXA2 had increased relapses (59 vs. 79%, p = 0.024, log-rank test) that revealed an independent prognostic value (HR = 3.29, C.I.95% = 1.45-7.45, p = 0.004, Cox regression). Our results suggest that FOXA2 promotes cell proliferation, maintains cancer stem cells, favors the development of Triple-Negative/Basal-like
tumors, and is associated with increase relapses.