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FOXM1 promotes the progression of prostate cancer by regulating PSA gene transcription
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 dete...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5370019/ https://www.ncbi.nlm.nih.gov/pubmed/28199985 http://dx.doi.org/10.18632/oncotarget.15224 |
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author | Liu, Youhong Liu, Yijun Yuan, Bowen Yin, Linglong Peng, Yuchong Yu, Xiaohui Zhou, Weibing Gong, Zhicheng Liu, Jianye He, Leye Li, Xiong |
author_facet | Liu, Youhong Liu, Yijun Yuan, Bowen Yin, Linglong Peng, Yuchong Yu, Xiaohui Zhou, Weibing Gong, Zhicheng Liu, Jianye He, Leye Li, Xiong |
author_sort | Liu, Youhong |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5370019 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53700192017-04-17 FOXM1 promotes the progression of prostate cancer by regulating PSA gene transcription Liu, Youhong Liu, Yijun Yuan, Bowen Yin, Linglong Peng, Yuchong Yu, Xiaohui Zhou, Weibing Gong, Zhicheng Liu, Jianye He, Leye Li, Xiong Oncotarget Research Paper 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. Impact Journals LLC 2017-02-09 /pmc/articles/PMC5370019/ /pubmed/28199985 http://dx.doi.org/10.18632/oncotarget.15224 Text en Copyright: © 2017 Liu et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Liu, Youhong Liu, Yijun Yuan, Bowen Yin, Linglong Peng, Yuchong Yu, Xiaohui Zhou, Weibing Gong, Zhicheng Liu, Jianye He, Leye Li, Xiong FOXM1 promotes the progression of prostate cancer by regulating PSA gene transcription |
title | FOXM1 promotes the progression of prostate cancer by regulating PSA gene transcription |
title_full | FOXM1 promotes the progression of prostate cancer by regulating PSA gene transcription |
title_fullStr | FOXM1 promotes the progression of prostate cancer by regulating PSA gene transcription |
title_full_unstemmed | FOXM1 promotes the progression of prostate cancer by regulating PSA gene transcription |
title_short | FOXM1 promotes the progression of prostate cancer by regulating PSA gene transcription |
title_sort | foxm1 promotes the progression of prostate cancer by regulating psa gene transcription |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5370019/ https://www.ncbi.nlm.nih.gov/pubmed/28199985 http://dx.doi.org/10.18632/oncotarget.15224 |
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