One of the most effected genes in the human tumors is p53. About 60% of human cancers contain mutation in p53 gene. Although the regulation of p53 is well studied, very little is known about the regulation of mutant p53. We have shown previously that a human B-lymphoma cell line (RL) harboring mutant p53, which is refractory to the growth inhibitory effects of transforming growth factor-beta (TGF-beta),can be rendered sensitive to TGF-beta by induction of receptors for TGF-beta with low concentrations of phorbol myristate acetate (PMA). We have also shown the growth inhibitory effect of TGF-beta was associated with a down regulation of mutant p53. Our goal is to understand the mechanisms involved in the down regulation of mutant p53 by TGF-beta, and to examine whether the down regulation of mutant p53 is responsible for the TGF-beta-mediated growth suppression. We are also interested in identifying the gain-of-function properties of mutant p53 in RL cells. The mutant p53 from RL and wild type p53 will be transfected separately in a human colon tumor cell line, HCT 116, which has p53 null background. The RNA from these cells will be used in micro array analysis using home made cDNA array chip to examine the expression pattern of several thousand genes. Genes that are differentially regulated by different p53 will be identified, and the roles of some of the candidate genes will studied.
| O'Farrell, Thomas J; Ghosh, Paritosh; Dobashi, Nobuaki et al. (2004) Comparison of the effect of mutant and wild-type p53 on global gene expression. Cancer Res 64:8199-207 |
