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Modulators of Prostate Cancer Cell Proliferation and Viability Identified by Short-Hairpin RNA Library Screening
There is significant need to identify novel prostate cancer drug targets because current hormone therapies eventually fail, leading to a drug-resistant and fatal disease termed castration-resistant prostate cancer. To functionally identify genes that, when silenced, decrease prostate cancer cell pro...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3324507/ https://www.ncbi.nlm.nih.gov/pubmed/22509301 http://dx.doi.org/10.1371/journal.pone.0034414 |
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author | Dahlman, Kimberly Brown Parker, Joel S. Shamu, Tambudzai Hieronymus, Haley Chapinski, Caren Carver, Brett Chang, Kenneth Hannon, Gregory J. Sawyers, Charles L. |
author_facet | Dahlman, Kimberly Brown Parker, Joel S. Shamu, Tambudzai Hieronymus, Haley Chapinski, Caren Carver, Brett Chang, Kenneth Hannon, Gregory J. Sawyers, Charles L. |
author_sort | Dahlman, Kimberly Brown |
collection | PubMed |
description | There is significant need to identify novel prostate cancer drug targets because current hormone therapies eventually fail, leading to a drug-resistant and fatal disease termed castration-resistant prostate cancer. To functionally identify genes that, when silenced, decrease prostate cancer cell proliferation or induce cell death in combination with antiandrogens, we employed an RNA interference-based short hairpin RNA barcode screen in LNCaP human prostate cancer cells. We identified and validated four candidate genes (AKT1, PSMC1, STRADA, and TTK) that impaired growth when silenced in androgen receptor positive prostate cancer cells and enhanced the antiproliferative effects of antiandrogens. Inhibition of AKT with a pharmacologic inhibitor also induced apoptosis when combined with antiandrogens, consistent with recent evidence for PI3K and AR pathway crosstalk in prostate cancer cells. Recovery of hairpins targeting a known prostate cancer pathway validates the utility of shRNA library screening in prostate cancer as a broad strategy to identify new candidate drug targets. |
format | Online Article Text |
id | pubmed-3324507 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33245072012-04-16 Modulators of Prostate Cancer Cell Proliferation and Viability Identified by Short-Hairpin RNA Library Screening Dahlman, Kimberly Brown Parker, Joel S. Shamu, Tambudzai Hieronymus, Haley Chapinski, Caren Carver, Brett Chang, Kenneth Hannon, Gregory J. Sawyers, Charles L. PLoS One Research Article There is significant need to identify novel prostate cancer drug targets because current hormone therapies eventually fail, leading to a drug-resistant and fatal disease termed castration-resistant prostate cancer. To functionally identify genes that, when silenced, decrease prostate cancer cell proliferation or induce cell death in combination with antiandrogens, we employed an RNA interference-based short hairpin RNA barcode screen in LNCaP human prostate cancer cells. We identified and validated four candidate genes (AKT1, PSMC1, STRADA, and TTK) that impaired growth when silenced in androgen receptor positive prostate cancer cells and enhanced the antiproliferative effects of antiandrogens. Inhibition of AKT with a pharmacologic inhibitor also induced apoptosis when combined with antiandrogens, consistent with recent evidence for PI3K and AR pathway crosstalk in prostate cancer cells. Recovery of hairpins targeting a known prostate cancer pathway validates the utility of shRNA library screening in prostate cancer as a broad strategy to identify new candidate drug targets. Public Library of Science 2012-04-11 /pmc/articles/PMC3324507/ /pubmed/22509301 http://dx.doi.org/10.1371/journal.pone.0034414 Text en Dahlman et al. http://creativecommons.org/licenses/by/4.0/ 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 properly credited. |
spellingShingle | Research Article Dahlman, Kimberly Brown Parker, Joel S. Shamu, Tambudzai Hieronymus, Haley Chapinski, Caren Carver, Brett Chang, Kenneth Hannon, Gregory J. Sawyers, Charles L. Modulators of Prostate Cancer Cell Proliferation and Viability Identified by Short-Hairpin RNA Library Screening |
title | Modulators of Prostate Cancer Cell Proliferation and Viability Identified by Short-Hairpin RNA Library Screening |
title_full | Modulators of Prostate Cancer Cell Proliferation and Viability Identified by Short-Hairpin RNA Library Screening |
title_fullStr | Modulators of Prostate Cancer Cell Proliferation and Viability Identified by Short-Hairpin RNA Library Screening |
title_full_unstemmed | Modulators of Prostate Cancer Cell Proliferation and Viability Identified by Short-Hairpin RNA Library Screening |
title_short | Modulators of Prostate Cancer Cell Proliferation and Viability Identified by Short-Hairpin RNA Library Screening |
title_sort | modulators of prostate cancer cell proliferation and viability identified by short-hairpin rna library screening |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3324507/ https://www.ncbi.nlm.nih.gov/pubmed/22509301 http://dx.doi.org/10.1371/journal.pone.0034414 |
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