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Modulation of the vitamin D3 response by cancer-associated mutant p53.

ABSTRACT: The p53 gene is mutated in many human tumors. Cells of such tumors often contain abundant mutant p53 (mutp53) protein, which may contribute actively to tumor progression via a gain-of-function mechanism. We applied ChIP-on-chip analysis and identified the vitamin D receptor (VDR) response element as overrepresented in promoter sequences bound by mutp53. We report that mutp53 can interact functionally and physically with VDR. Mutp53 is recruited to VDR-regulated genes and modulates their expression, augmenting the transactivation of some genes and relieving the repression of others. Furthermore, mutp53 increases the nuclear accumulation of VDR. Importantly, mutp53 converts vitamin D into an antiapoptotic agent. Thus, p53 status can determine the biological impact of vitamin D on tumor cells.

SUBMITTER: Stambolsky P

PROVIDER: S-EPMC2882298 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Modulation of the vitamin D3 response by cancer-associated mutant p53.

Stambolsky Perry P Tabach Yuval Y Fontemaggi Giulia G Weisz Lilach L Maor-Aloni Revital R Siegfried Zehava Z Shiff Idit I Kogan Ira I Shay Moshe M Kalo Eyal E Blandino Giovanni G Simon Itamar I Oren Moshe M Rotter Varda V

Cancer cell 20100301 3

The p53 gene is mutated in many human tumors. Cells of such tumors often contain abundant mutant p53 (mutp53) protein, which may contribute actively to tumor progression via a gain-of-function mechanism. We applied ChIP-on-chip analysis and identified the vitamin D receptor (VDR) response element as overrepresented in promoter sequences bound by mutp53. We report that mutp53 can interact functionally and physically with VDR. Mutp53 is recruited to VDR-regulated genes and modulates their expressi ...[more]

PMID: 20227041

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