FOXP1, an Estrogen-Inducible Transcription Factor, Modulates Cell Proliferation in Breast Cancer Cells and 5-Year Recurrence-Free Survival of Patients with Tamoxifen-Treated Breast Cancer

Abstract

Breast cancer is primarily a hormone-dependent tumor that can be regulated by the status of steroid hormones, including estrogen and progesterone. 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. In the present study, we investigated the expression of FOXP1 in 133 human invasive breast cancers, obtained by core biopsy, by immunohistochemical analysis. Nuclear immunoreactivity of FOXP1 was detected in 89 cases (67%) and correlated positively with tumor grade and hormone receptor status, including estrogen receptor alpha (ERα) and progesterone receptor, and negatively with pathological tumor size. In ERα-positive MCF-7 breast cancer cells, we demonstrated that FOXP1 mRNA was upregulated by estrogen and increased ERα recruitment to ER binding sites identified by ChIP-on-chip analysis within the FOXP1 gene region. We also demonstrated that proliferation of MCF-7 cells was increased by exogenously transfected FOXP1 and decreased by FOXP1-specific siRNA. Furthermore, FOXP1 enhanced estrogen response element-driven transcription in MCF-7 cells. Finally, FOXP1 immunoreactivity was sig-

WITHDRAWN: Correlation between FOXP1 and ER/PR expression in endometrial carcinoma

“…In breast cancer, FOXP1 is an estrogen-induced transcriptional factor and its expression is associated with ERα, ERβ and the PR [7,19]. In order to confirm a similar role for FOXP1 in endometrial carcinoma, we exposed Ishikawa cells to increasing concentrations of estradiol and then measured the expression of FOXP1, ERα, ERβ and PR.…”

“…FOXP1 and ER can thus mutually regulate their transcription [7,18]. In previous studies of breast cancer, it was found that estradiol formed a complex with ER, CoR(nucleus receptor coactivator 1) and AP1(AP-1 transcription factor subunit)/SP1(Transcription factor Sp1).…”

“…ChIP assay and quantitative real-time reversed transcription polymerase chain reaction were performed as previously described [7]. Ishikawa cells were fixed in 37% formaldehyde for 10 min at room temperature.…”

“…It plays an important role in the regulation of B cell development and monocyte differentiation, and participates in cardiac valve morphodifferentiation and lung development [4]. Numerous studies have shown that the expression level of FOXP1 shows a marked change in tumor tissues, being lower in renal, breast, ovarian, lung and prostate cancers than in normal tissues [5][6][7][8][9][10], but is increased in malignant tumors such as lymphoma, which indicates that FOXP1 may have other roles except as an anti-oncogene [11][12][13].…”

Expression of FOXP1 in epithelial ovarian cancer (EOC) and its correlation with chemotherapy resistance and prognosis

“…Further research revealed loss or ectopic cytoplasmic expression of FOXP1 in several solid tumors, and its expression was closely related to the steroid hormone receptor signaling pathway. Nevertheless, there are no studies assessing the relationship between FOXP1 expression and the malignant biological behaviors of ovarian tumors [10,11].…”