Inhibitor of differentiation 4 Id4 is a potential tumor suppressor in prostate cancerReport as inadecuate

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BMC Cancer

, 9:173

First Online: 07 June 2009Received: 31 July 2008Accepted: 07 June 2009DOI: 10.1186-1471-2407-9-173

Cite this article as: Carey, J.P., Asirvatham, A.J., Galm, O. et al. BMC Cancer 2009 9: 173. doi:10.1186-1471-2407-9-173


BackgroundInhibitor of differentiation 4 Id4, a member of the Id gene family is also a dominant negative regulator of basic helix loop helix bHLH transcription factors. Some of the functions of Id4 appear to be unique as compared to its other family members Id1, Id2 and Id3. Loss of Id4 gene expression in many cancers in association with promoter hypermethylation has led to the proposal that Id4 may act as a tumor suppressor. In this study we provide functional evidence that Id4 indeed acts as a tumor suppressor and is part of a cancer associated epigenetic re-programming.

MethodsData mining was used to demonstrate Id4 expression in prostate cancer. Methylation specific polymerase chain reaction MSP analysis was performed to understand molecular mechanisms associated with Id4 expression in prostate cancer cell lines. The effect of ectopic Id4 expression in DU145 cells was determined by cell cycle analysis 3H thymidine incorporation and FACS, expression of androgen receptor, p53 and cyclin dependent kinase inhibitors p27 and p21 by a combination of RT-PCR, real time-PCR, western blot and immuno-cytochemical analysis.

ResultsId4 expression was down-regulated in prostate cancer. Id4 expression was also down-regulated in prostate cancer line DU145 due to promoter hyper-methylation. Ectopic Id4 expression in DU145 prostate cancer cell line led to increased apoptosis and decreased cell proliferation due in part by an S-phase arrest. In addition to S-phase arrest, ectopic Id4 expression in PC3 cells also resulted in prolonged G2-M phase. At the molecular level these changes were associated with increased androgen receptor AR, p21, p27 and p53 expression in DU145 cells.

ConclusionThe results suggest that Id4 acts directly as a tumor suppressor by influencing a hierarchy of cellular processes at multiple levels that leads to a decreased cell proliferation and change in morphology that is possibly mediated through induction of previously silenced tumor suppressors.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-9-173 contains supplementary material, which is available to authorized users.

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Author: Jason PW Carey - Ananthi J Asirvatham - Oliver Galm - Tandeih A Ghogomu - Jaideep Chaudhary


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