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|Title:||Evidence of a novel antiapoptotic factor: Role of inhibitor of differentiation or DNA binding (Id-1) in anticancer drug-induced apoptosis|
|Authors:||Zhang, X;Ling, MT;Wong, YC;Wang, X|
|Publisher:||Blackwell Publishing Japan. The Journal's web site is located at http://www.blackwellpublishing.com/journals/CAS|
|Description:||Id-1 (inhibitor of differentiation or DNA binding), a member of the basic helix-loop-helix transcription factor family, is up-regulated in many types of human cancer and its expression levels are correlated with poor treatment outcome and shorter survival. In this study, we provided evidence to suggest that Id-1 is a universal survival factor that plays a key role in protection against anticancer drug-induced apoptosis. Using nine anticancer drugs and five cancer cell lines derived from nasopharyngeal carcinoma (CNE1), cervical carcinoma (HeLa), breast cancer (MCF7), hepatocarcinoma (Huh7) and prostate cancer (PC3), we found that down-regulation of Id-1 expression at both transcriptional and protein levels was associated with increased apoptosis rates and increased cleaved PARP after exposure to all anticancer agents. Treatment with a caspase 9 inhibitor, Z-LEHD-FMK, protected cancer cells from drug-induced PARP cleavage. However, overexpression of Id-1 in a p53 mutated cell line, CNE1, was able to suppress PARP cleavage in response to all anticancer drugs examined. In contrast, down-regulation of Id-1 through small RNA technology in CNE1 cells led to increased sensitivity to all six types of chemotherapeutic drugs. Our results demonstrate that Id-1 may be a general negative regulator of anticancer drug-induced apoptosis and suggest a novel therapeutic target in inducing chemosensitization in cancer cells. Our evidence also provides a possible underlying mechanism responsible for the positive role of Id-1 in the progression of human cancer. © 2007 Japanese Cancer Association.|
|Standard no:||Cancer Science, 2007, v. 98 n. 3, p. 308-314|
|Appears in Collections:||Department of Anatomy|
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