title: FOXM1 promotes the progression of prostate cancer by regulating PSA gene transcription.
abstract: Androgen/AR is the primary contributor to prostate cancer (PCa) progression by regulating Prostate Specific Antigen (PSA) gene transcription. The disease inevitably evolves to androgen-independent (AI) status. Other mechanisms by which PSA is regulated and develops to AI have not yet been fully determined. FOXM1 is a cell proliferation-specific transcription factor highly expressed in PCa cells compared to non-malignant prostate epithelial cells, suggesting that the aberrant overexpression of FOXM1 contributes to PCa development. In addition to regulating AR gene transcription and cell cycle-regulatory genes, FOXM1 selectively regulates the gene transcription of KLK2 and PSA, typical androgen responsive genes. Screening the potential FOXM1-binding sites by ChIP-PCR, we found that FOXM1 directly binds to the FHK binding motifs in the PSA promoter/enhancer regions. AI C4-2 cells have more FOXM1 binding sites than androgen dependent LNCaP cells. The depletion of FOXM1 by small molecular inhibitors significantly improves the suppression of PSA gene transcription by the anti-AR agent Cadosax. This is the first report showing that FOXM1 promotes PCa progression by regulating PSA gene transcription, particularly in AI PCa cells. The combination of anti-AR agents and FOXM1 inhibitors has the potential to greatly improve therapy for late-stage PCa patients by suppressing PSA levels.
authors.affiliation: Center for Molecular Medicine, Xiangya Hospital, Central South University, China.|Hunan Key Laboratory of Molecular Radiation Oncology, Xiangya Hospital, Central South University, China.
authors.forename: Youhong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Center for Molecular Medicine, Xiangya Hospital, Central South University, China.|Hunan Key Laboratory of Molecular Radiation Oncology, Xiangya Hospital, Central South University, China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Center for Molecular Medicine, Xiangya Hospital, Central South University, China.|Hunan Key Laboratory of Molecular Radiation Oncology, Xiangya Hospital, Central South University, China.
authors.forename: Bowen
authors.initials: B
authors.lastname: Yuan
authors.affiliation: Center for Molecular Medicine, Xiangya Hospital, Central South University, China.|Hunan Key Laboratory of Molecular Radiation Oncology, Xiangya Hospital, Central South University, China.
authors.forename: Linglong
authors.initials: L
authors.lastname: Yin
authors.affiliation: Center for Molecular Medicine, Xiangya Hospital, Central South University, China.|Hunan Key Laboratory of Molecular Radiation Oncology, Xiangya Hospital, Central South University, China.
authors.forename: Yuchong
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Center for Molecular Medicine, Xiangya Hospital, Central South University, China.|Hunan Key Laboratory of Molecular Radiation Oncology, Xiangya Hospital, Central South University, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Oncology, Xiangya Hospital, Central South University, China.
authors.forename: Weibing
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Pharmacy, Xiangya Hospital, Central South University, China.
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Gong
authors.affiliation: Department of Urology, The Third Xiangya Hospital, Central South University, China.|Research Institute of Prostate Diseases, Central South University, China.
authors.forename: Jianye
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Urology, The Third Xiangya Hospital, Central South University, China.|Research Institute of Prostate Diseases, Central South University, China.
authors.forename: Leye
authors.initials: L
authors.lastname: He
authors.affiliation: Center for Molecular Medicine, Xiangya Hospital, Central South University, China.|Hunan Key Laboratory of Molecular Radiation Oncology, Xiangya Hospital, Central South University, China.|Research Institute of Prostate Diseases, Central South University, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Li
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D018450:Disease Progression; D000072278:Forkhead Box Protein M1 / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism; D008297:Male; D011401:Promoter Regions, Genetic / Q000235:genetics; D017430:Prostate-Specific Antigen / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D034622:RNA Interference; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D011944:Receptors, Androgen; C000595667:KLK2 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: FOXM1; PSA; androgen receptor; gene transcription; prostate cancer