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The DACH1 gene is frequently deleted in prostate cancer, restrains prostatic intraepithelial neoplasia, decreases DNA damage repair, and predicts therapy responses
Prostate cancer (PCa), the second leading cause of death in American men, includes distinct genetic subtypes with distinct therapeutic vulnerabilities. The DACH1 gene encodes a winged helix/Forkhead DNA-binding protein that competes for binding to FOXM1 sites. Herein, DACH1 gene deletion within the...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Journal Experts
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9882663/ https://www.ncbi.nlm.nih.gov/pubmed/36712010 http://dx.doi.org/10.21203/rs.3.rs-2423179/v1 |
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author | Li, Zhiping Jiao, Xuanmao Robertson, A. Gordon Sante, Gabriele Di Ashton, Anthony W. DiRocco, Agnese Wang, Min Zhao, Jun Addya, Sankar Wang, Chenguang McCue, Peter A. South, Andrew P. Cordon-Cardo, Carlos Liu, Runzhi Patel, Kishan Hamid, Rasha Parmar, Jorim DuHadaway, James B. Jones, Steven J. Casimiro, Mathew C. Schultz, Nikolaus Kossenkov, Andrew Phoon, Lai Yee Chen, Hao Lan, Li Sun, Yunguang Iczkowski, Kenneth A. Rui, Hallgeir Pestell, Richard G. |
author_facet | Li, Zhiping Jiao, Xuanmao Robertson, A. Gordon Sante, Gabriele Di Ashton, Anthony W. DiRocco, Agnese Wang, Min Zhao, Jun Addya, Sankar Wang, Chenguang McCue, Peter A. South, Andrew P. Cordon-Cardo, Carlos Liu, Runzhi Patel, Kishan Hamid, Rasha Parmar, Jorim DuHadaway, James B. Jones, Steven J. Casimiro, Mathew C. Schultz, Nikolaus Kossenkov, Andrew Phoon, Lai Yee Chen, Hao Lan, Li Sun, Yunguang Iczkowski, Kenneth A. Rui, Hallgeir Pestell, Richard G. |
author_sort | Li, Zhiping |
collection | PubMed |
description | Prostate cancer (PCa), the second leading cause of death in American men, includes distinct genetic subtypes with distinct therapeutic vulnerabilities. The DACH1 gene encodes a winged helix/Forkhead DNA-binding protein that competes for binding to FOXM1 sites. Herein, DACH1 gene deletion within the 13q21.31-q21.33 region occurs in up to 18% of human PCa and was associated with increased AR activity and poor prognosis. In prostate OncoMice, prostate-specific deletion of the Dach1 gene enhanced prostatic intraepithelial neoplasia (PIN), and was associated with increased TGFβ activity and DNA damage. Reduced Dach1 increased DNA damage in response to genotoxic stresses. DACH1 was recruited to sites of DNA damage, augmenting recruitment of Ku70/Ku80. Reduced Dach1 expression was associated with increased homology directed repair and resistance to PARP inhibitors and TGFβ kinase inhibitors. Reduced Dach1 expression may define a subclass of PCa that warrants specific therapies. |
format | Online Article Text |
id | pubmed-9882663 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Journal Experts |
record_format | MEDLINE/PubMed |
spelling | pubmed-98826632023-01-28 The DACH1 gene is frequently deleted in prostate cancer, restrains prostatic intraepithelial neoplasia, decreases DNA damage repair, and predicts therapy responses Li, Zhiping Jiao, Xuanmao Robertson, A. Gordon Sante, Gabriele Di Ashton, Anthony W. DiRocco, Agnese Wang, Min Zhao, Jun Addya, Sankar Wang, Chenguang McCue, Peter A. South, Andrew P. Cordon-Cardo, Carlos Liu, Runzhi Patel, Kishan Hamid, Rasha Parmar, Jorim DuHadaway, James B. Jones, Steven J. Casimiro, Mathew C. Schultz, Nikolaus Kossenkov, Andrew Phoon, Lai Yee Chen, Hao Lan, Li Sun, Yunguang Iczkowski, Kenneth A. Rui, Hallgeir Pestell, Richard G. Res Sq Article Prostate cancer (PCa), the second leading cause of death in American men, includes distinct genetic subtypes with distinct therapeutic vulnerabilities. The DACH1 gene encodes a winged helix/Forkhead DNA-binding protein that competes for binding to FOXM1 sites. Herein, DACH1 gene deletion within the 13q21.31-q21.33 region occurs in up to 18% of human PCa and was associated with increased AR activity and poor prognosis. In prostate OncoMice, prostate-specific deletion of the Dach1 gene enhanced prostatic intraepithelial neoplasia (PIN), and was associated with increased TGFβ activity and DNA damage. Reduced Dach1 increased DNA damage in response to genotoxic stresses. DACH1 was recruited to sites of DNA damage, augmenting recruitment of Ku70/Ku80. Reduced Dach1 expression was associated with increased homology directed repair and resistance to PARP inhibitors and TGFβ kinase inhibitors. Reduced Dach1 expression may define a subclass of PCa that warrants specific therapies. American Journal Experts 2023-01-10 /pmc/articles/PMC9882663/ /pubmed/36712010 http://dx.doi.org/10.21203/rs.3.rs-2423179/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. |
spellingShingle | Article Li, Zhiping Jiao, Xuanmao Robertson, A. Gordon Sante, Gabriele Di Ashton, Anthony W. DiRocco, Agnese Wang, Min Zhao, Jun Addya, Sankar Wang, Chenguang McCue, Peter A. South, Andrew P. Cordon-Cardo, Carlos Liu, Runzhi Patel, Kishan Hamid, Rasha Parmar, Jorim DuHadaway, James B. Jones, Steven J. Casimiro, Mathew C. Schultz, Nikolaus Kossenkov, Andrew Phoon, Lai Yee Chen, Hao Lan, Li Sun, Yunguang Iczkowski, Kenneth A. Rui, Hallgeir Pestell, Richard G. The DACH1 gene is frequently deleted in prostate cancer, restrains prostatic intraepithelial neoplasia, decreases DNA damage repair, and predicts therapy responses |
title | The DACH1 gene is frequently deleted in prostate cancer, restrains prostatic intraepithelial neoplasia, decreases DNA damage repair, and predicts therapy responses |
title_full | The DACH1 gene is frequently deleted in prostate cancer, restrains prostatic intraepithelial neoplasia, decreases DNA damage repair, and predicts therapy responses |
title_fullStr | The DACH1 gene is frequently deleted in prostate cancer, restrains prostatic intraepithelial neoplasia, decreases DNA damage repair, and predicts therapy responses |
title_full_unstemmed | The DACH1 gene is frequently deleted in prostate cancer, restrains prostatic intraepithelial neoplasia, decreases DNA damage repair, and predicts therapy responses |
title_short | The DACH1 gene is frequently deleted in prostate cancer, restrains prostatic intraepithelial neoplasia, decreases DNA damage repair, and predicts therapy responses |
title_sort | dach1 gene is frequently deleted in prostate cancer, restrains prostatic intraepithelial neoplasia, decreases dna damage repair, and predicts therapy responses |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9882663/ https://www.ncbi.nlm.nih.gov/pubmed/36712010 http://dx.doi.org/10.21203/rs.3.rs-2423179/v1 |
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