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Article: Inactivation Of Atm/atr Dna Damage Checkpoint Promotes Androgen Induced Chromosomal Instability In Prostate Epithelial Cells.

TitleInactivation Of Atm/atr Dna Damage Checkpoint Promotes Androgen Induced Chromosomal Instability In Prostate Epithelial Cells.
Authors
Issue Date2012
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2012, v. 7 n. 12, p. e51108 How to Cite?
AbstractThe ATM/ATR DNA damage checkpoint functions in the maintenance of genetic stability and some missense variants of the ATM gene have been shown to confer a moderate increased risk of prostate cancer. However, whether inactivation of this checkpoint contributes directly to prostate specific cancer predisposition is still unknown. Here, we show that exposure of non-malignant prostate epithelial cells (HPr-1AR) to androgen led to activation of the ATM/ATR DNA damage response and induction of cellular senescence. Notably, knockdown of the ATM gene expression in HPr-1AR cells can promote androgen-induced TMPRSS2: ERG rearrangement, a prostate-specific chromosome translocation frequently found in prostate cancer cells. Intriguingly, unlike the non-malignant prostate epithelial cells, the ATM/ATR DNA damage checkpoint appears to be defective in prostate cancer cells, since androgen treatment only induced a partial activation of the DNA damage response. This mechanism appears to preserve androgen induced autophosphorylation of ATM and phosphorylation of H2AX, lesion processing and repair pathway yet restrain ATM/CHK1/CHK2 and p53 signaling pathway. Our findings demonstrate that ATM/ATR inactivation is a crucial step in promoting androgen-induced genomic instability and prostate carcinogenesis.
Persistent Identifierhttp://hdl.handle.net/10722/185624
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorChiu, YT-
dc.contributor.authorLiu, J-
dc.contributor.authorTang, K-
dc.contributor.authorWong, YC-
dc.contributor.authorLing, MT-
dc.date.accessioned2013-08-20T11:34:42Z-
dc.date.available2013-08-20T11:34:42Z-
dc.date.issued2012-
dc.identifier.citationPlos One, 2012, v. 7 n. 12, p. e51108-
dc.identifier.issn1932-6203-
dc.identifier.urihttp://hdl.handle.net/10722/185624-
dc.description.abstractThe ATM/ATR DNA damage checkpoint functions in the maintenance of genetic stability and some missense variants of the ATM gene have been shown to confer a moderate increased risk of prostate cancer. However, whether inactivation of this checkpoint contributes directly to prostate specific cancer predisposition is still unknown. Here, we show that exposure of non-malignant prostate epithelial cells (HPr-1AR) to androgen led to activation of the ATM/ATR DNA damage response and induction of cellular senescence. Notably, knockdown of the ATM gene expression in HPr-1AR cells can promote androgen-induced TMPRSS2: ERG rearrangement, a prostate-specific chromosome translocation frequently found in prostate cancer cells. Intriguingly, unlike the non-malignant prostate epithelial cells, the ATM/ATR DNA damage checkpoint appears to be defective in prostate cancer cells, since androgen treatment only induced a partial activation of the DNA damage response. This mechanism appears to preserve androgen induced autophosphorylation of ATM and phosphorylation of H2AX, lesion processing and repair pathway yet restrain ATM/CHK1/CHK2 and p53 signaling pathway. Our findings demonstrate that ATM/ATR inactivation is a crucial step in promoting androgen-induced genomic instability and prostate carcinogenesis.-
dc.languageeng-
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action-
dc.relation.ispartofPlos One-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleInactivation Of Atm/atr Dna Damage Checkpoint Promotes Androgen Induced Chromosomal Instability In Prostate Epithelial Cells.-
dc.typeArticle-
dc.identifier.emailWong, YC: ycwong@hkucc.hku.hk-
dc.identifier.emailLing, MT: patling@hkucc.hku.hk-
dc.identifier.authorityWong, YC=rp00316-
dc.identifier.authorityLing, MT=rp00449-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0051108-
dc.identifier.pmcidPMC3525593-
dc.identifier.hkuros218411-
dc.identifier.volume7-
dc.identifier.issue12-
dc.identifier.spagee51108-
dc.identifier.epagee51108-
dc.publisher.placeUnited States-

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