| Literature DB >> 15077194 |
Mariano J Scian1, Katherine E R Stagliano, Debabrita Deb, Michelle A Ellis, Evie H Carchman, Anindita Das, Kristopher Valerie, Swati Palit Deb, Sumitra Deb.
Abstract
We have studied the mechanism of mutant p53-mediated oncogenesis using several tumor-derived mutants. Using a colony formation assay, we found that the majority of the mutants increased the number of colonies formed compared to the vector. Expression of tumor-derived p53 mutants increases the rate of cell growth, suggesting that the p53 mutants have 'gain of function' properties. We have studied the gene expression profile of cells expressing tumor-derived p53-D281G to identify genes transactivated by mutant p53. We report the transactivation of two genes, asparagine synthetase and human telomerase reverse transcriptase. Quantitative real-time PCR confirms this upregulation. Transient transfection promoter assays verify that tumor-derived p53 mutants transactivate these promoters significantly. An electrophoretic mobility shift assay shows that tumor-derived p53-mutants cannot bind to the wild-type p53 consensus sequence. The results presented here provide some evidence of a possible mechanism for mutant p53-mediated transactivation.Entities:
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Year: 2004 PMID： 15077194 DOI： 10.1038/sj.onc.1207553
Source DB: PubMed Journal: Oncogene ISSN： 0950-9232 Impact factor: 9.867