The expression of the transcription factor FOXA1 is associated with the prognosis of estrogen receptor (ER)-positive breast cancer, and the genetic variant rs4442975 can affect FOXA1 function.
To improve the non-invasive therapeutic efficacy for ER positive breast cancer (ER+ BC), we fabricated a multifunctional FOXA1 loaded porphyrin microbubble to combine photodynamic therapy (PDT) and gene therapy of FOXA1 knockdown (KD) with ultrasound targeted microbubble destruction (UTMD) technology under the guidance of contrast enhanced ultrasound (CEUS).
These results demonstrate that FOXA1 as a potent survival factor that suppresses TGF-β-induced apoptosis by inhibiting Smad3 signaling in estrogen receptor-positive breast cancer cells.
Because FOXA1 regulates a luminal gene expression signature in progenitor cells and represses the basal phenotype, this could be a mechanism that links these reproductive exposures with ER- breast cancer.
Forkhead box A1 (FOXA1) is a member of the forkhead box transcription factor family and functions as a pioneer factor in estrogen receptor (ER)-positive breast cancer.
These results demonstrate a novel pathway of ER and FOXA1 transcription factor crosstalk in regulating RET/PTC kinase expression, and demonstrate that RET/PTC kinase is a critical regulator for the proliferation of ER-positive breast cancer cells.
A statistically significant correlation between the Oncotype DX recurrence scores and FOXA1 expression in our diverse cohort of ER-positive breast cancer patients was observed.
Taken together, our results reveal an estrogen-regulated combinatorial network including cell-specific cis- and trans-regulators of CCND1 expression where ERalpha collaborates with other transcription factors associated with the ER-positive breast cancer phenotype, including FoxA1 and NFIC.