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dc.contributor.authorCasimiro, M
dc.contributor.authorDi Sante, G
dc.contributor.authorJu, X
dc.contributor.authorLi, Z
dc.contributor.authorChen, K
dc.contributor.authorCrosariol, M
dc.contributor.authorYaman, I
dc.contributor.authorGormley, M
dc.contributor.authorMeng, H
dc.contributor.authorLisanti, Michael P
dc.contributor.authorPestell, R
dc.date.accessioned2016-01-06T10:44:01Zen
dc.date.available2016-01-06T10:44:01Zen
dc.date.issued2015-11-18en
dc.identifier.citationCyclin D1 promotes androgen-dependent DNA damage repair in prostate cancer cells. 2015: Cancer Resen
dc.identifier.issn1538-7445en
dc.identifier.pmid26582866en
dc.identifier.doi10.1158/0008-5472.CAN-15-0999en
dc.identifier.urihttp://hdl.handle.net/10541/592943en
dc.description.abstractTherapy resistance and poor outcome in prostate cancer is associated with increased expression of Cyclin D1. Androgens promote DNA double strand break repair to reduce DNA damage, and cyclin D1 was also shown to enhance DNA damage repair (DDR). In this study, we investigated the significance of cyclin D1 in androgen-induced DDR using established prostate cancer cells and prostate tissues from cyclinD1 knockout mice. We demonstrate that endogenous cyclin D1 further diminished the dihydrotestosterone (DHT)-dependent reduction of gammaH2AX foci in vitro. We also show that cyclin D1 was required for the androgen-dependent DNA damage response both in vitro and in vivo. Furthermore, cyclin D1 was required for androgen-enhanced DDR and radioresistance of prostate cancer cells. Moreover, microarray analysis of primary prostate epithelial cells from cyclin D1-deficient and wild-type mice demonstrated that most of the DHT-dependent gene expression changes are also cyclin D1-dependent. Collectively, our findings suggest that the hormone-mediated recruitment of cyclin D1 to sites of DDR may facilitate the resistance of prostate cancer cells to DNA damage therapies, and highlight the need to explore other therapeutic approaches in prostate cancer to prevent or overcome drug resistance.
dc.languageENGen
dc.language.isoenen
dc.rightsArchived with thanks to Cancer researchen
dc.titleCyclin D1 promotes androgen-dependent DNA damage repair in prostate cancer cells.en
dc.typeArticleen
dc.contributor.departmentCancer Biology, Thomas Jefferson University.en
dc.identifier.journalCancer Researchen
html.description.abstractTherapy resistance and poor outcome in prostate cancer is associated with increased expression of Cyclin D1. Androgens promote DNA double strand break repair to reduce DNA damage, and cyclin D1 was also shown to enhance DNA damage repair (DDR). In this study, we investigated the significance of cyclin D1 in androgen-induced DDR using established prostate cancer cells and prostate tissues from cyclinD1 knockout mice. We demonstrate that endogenous cyclin D1 further diminished the dihydrotestosterone (DHT)-dependent reduction of gammaH2AX foci in vitro. We also show that cyclin D1 was required for the androgen-dependent DNA damage response both in vitro and in vivo. Furthermore, cyclin D1 was required for androgen-enhanced DDR and radioresistance of prostate cancer cells. Moreover, microarray analysis of primary prostate epithelial cells from cyclin D1-deficient and wild-type mice demonstrated that most of the DHT-dependent gene expression changes are also cyclin D1-dependent. Collectively, our findings suggest that the hormone-mediated recruitment of cyclin D1 to sites of DDR may facilitate the resistance of prostate cancer cells to DNA damage therapies, and highlight the need to explore other therapeutic approaches in prostate cancer to prevent or overcome drug resistance.


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