Lookup NU author(s): Dr Ian Logan,
Dr Xiaohong Lu,
Professor John Lunec,
Professor Craig Robson
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BACKGROUND: Small molecule MDM2 antagonists including nutlin-3 have been shown to be effective against a range of cancer cell types and nutlin-3 can inhibit growth of LNCaP xenografts. We compared the efficacy of nutlin-3 in three prostate cancer cell types and provide an insight into the mechanism of nutlin-3. METHODS: Nutlin-3 efficacy was measured using proliferation assays, cell cycle analysis, apoptosis assays, quantitative RT-PCR, and immunoblotting. Chromatin immunoprecipitation (ChIP) assays were also performed. RESULTS: Nutlin-3 can specifically inhibit proliferation of LNCaP cells through cell cycle arrest and apoptosis. This coincides with increased levels of the p53-responsive transcripts p21, PUMA, gadd45, and Mdm2 and recruitment of p53 to chromatin. Nutlin-3 also reduces androgen receptor levels, resulting in altered receptor recruitment to chromatin. CONCLUSION: Our study demonstrates that small molecule MDM2 antagonists might be useful in the treatment of human prostate cancers that retain functional p53 and androgen receptor signaling. © 2007 Wiley-Liss, Inc.
Author(s): Logan, I., McNeill, H., Cook, S., Lu, X., Lunec, J., Robson, C.N.
Publication type: Article
Publication status: Published
Print publication date: 01/06/2007
ISSN (print): 0270-4137
ISSN (electronic): 1097-0045
PubMed id: 17440969
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