FOXA1 modulates EAF2 regulation of AR transcriptional activity, cell proliferation, and migration in prostate cancer cells.

摘要: BACKGROUND ELL-associated factor 2 (EAF2) is an androgen-regulated tumor suppressor in the prostate. However, mechanisms underlying suppressive function of EAF2 are still largely unknown. Identification factors capable modulating will help elucidate function. METHODS Using eaf-1(the ortholog EAF2) mutant C. elegans model, RNAi screen was used to identify on basis their knockdown synergistically enhance reduced fertility phenotype eaf-1 elegans. In human cells, interaction with FOXA1 and effect protein levels were determined by co-immunoprecipitation stability assay. The and/or expression AR-target genes real-time RT-PCR luciferase reporter assays. LNCaP prostate cancer cell proliferation migration tested using BrdU assay transwell assay. RESULTS RNAi identified pha-4, mammalian FOXA1, its causing sterility. co-immunoprecipitated FOXA1. enhanced endogenous level, whereas transfected GFP-EAF2 down-regulated protein. Also, genes, proliferation, cells. inhibited gene expression, suggesting that can modulate regulation AR transcriptional activation, migration. CONCLUSIONS These findings suggest signaling pathway, through represents important mechanism suppression carcinogenesis. Prostate 75:976–987, 2015. © 2015 Wiley Periodicals, Inc.