FOXP1 and estrogen signaling in breast cancer

Breast cancers are considered to be primarily regulated by estrogen signaling pathways because estrogen-dependent proliferation is observed in the majority of breast cancer cases. Thus, hormone therapy using antiestrogen drugs such as tamoxifen is effective for breast cancers expressing estrogen receptor α (ERα). However, acquired resistance during the endocrine therapy is a critical unresolved problem in breast cancer. Recently, a forkhead transcription factor FOXA1 has been reported to play an important role in the regulation of ERα-mediated transcription and proliferation of breast cancer. Interestingly, immunohistochemical analysis of breast cancer specimens has revealed that nuclear immunoreactivities of FOXP1 as well as those of FOXA1 are positively correlated with hormone receptor status, including ERα and progesterone receptor. In particular, the double-positive immunoreactivities of FOXP1 and FOXA1 are significantly associated with a favorable prognosis for survival of breast cancer patients receiving adjuvant tamoxifen therapy. The functions of FOXP1 and FOXA1 have been characterized in cultured cells; further, similar to FOXA1, FOXP1 is assumed to be a critical transcription factor for ERα signaling, and both forkhead transcription factors can serve as predictive factors for acquired endocrine resistance in breast cancer.