P4-01-21: An Estrogen-Inducible Transcription Factor FOXP1 Promotes Estrogen-Dependent Cell Proliferation of Breast Cancer Cells and Is Associated with 5-Year Disease-Free Survival in Patients with Tamoxifen-Treated Breast Cancer.

Abstract

Abstract Estrogen signaling pathways are involved in the growth and development of breast tumors through the activation of estrogen receptor a (ERα). ERα is expressed in most breast cancers and involves in estrogen-dependent proliferation by acting as transcription factors activating the expression of target genes. Various coregulators and transcription factors are associated with ERα-mediated transcriptional control of target genes. Therefore, a comprehensive understanding of estrogen signaling pathways in breast cancer is required for both treatment and diagnosis of the disease. Forkhead box P1 (FOXP1) is a member of the forkhead box transcription factor family and has been reported to be associated with various types of tumors. Here, we investigated the expression pattern of FOXP1 by immunohistochemistry in a series of 133 invasive breast cancers and compared it with clinicopathological factors. The expression of FOXP1 was detected in nuclei in 89 cases (67%) and correlated positively with tumor grade and hormone receptor status, including ERα and progesterone receptor (PgR), and negatively with pathological tumor size (pT). And in ERα-positive MCF-7 breast cancer cells, we demonstrated that FOXP1 mRNA was upregulated by estrogen and that ERα recruitment to ER binding sites within the FOXP1 gene region identified by ChIP-chip analysis was increased. We also demonstrated that proliferation of MCF-7 cells was increased by exogenously transfected FOXP1 and decreased by FOXP1-specific siRNA. Moreover, in MCF-7 cells, FOXP1 enhanced estrogen response element (ERE)-driven transcription. Finally, FOXP1 immunoreactivity was significantly more elevated in relapse-free breast cancer patients treated with tamoxifen than in relapse patients treated with it. Taken together, these results suggest that FOXP1 plays an important role in proliferation of breast cancer cells by modulating estrogen signaling and that FOXP1 immunoreactivity might be associated with the estrogen dependency of breast cancer clinically, which may predict favorable prognosis in the patients treated with tamoxifen. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-01-21.