S-Space College of Dentistry/School of Dentistry (치과대학/치의학대학원) Dept. of Dentistry (치의학과) Journal Papers (저널논문_치의학과)
Effect of p53 gene transfer on the cell proliferation and cell cycle progression in a human oral cancer cell line with p53 mutation
- Issue Date
- Korean Academy of Oral Biology
- Int. J. of Oral Biol. 23(4):189-199
- p53 mutation ; p53 gene-transfer ; tumorigenic phenotype ; cell cycle regulators ; oral squamous cell ; carcinoma cell line
- To investigate the effect of p53 gene transfer on the cell proliferation and cell cycle progression in an oral cancer cell line containing p53 mutation, we introduced a recombinant plasmid (pMSG-p53X) encoding wt p53 into SCC-9 line. A stable clonal cell line, SCC-9-p53X, was derived that conditionally expressed wt p53 protein following exposure to dexamethasone. Induction of wt p53 expression may play an improtant role in the suppression of tumorigenic phenotypes in cancer cells with p53 mutations by decreased expression and/or activities of key G_1-phase cell cycle regulatory proteins. To investigate this possibility, we determined the change of tumorigenic phenotype, the cellular levels of key G_1-phase cell cycle regulatory proteins p21^WAF1/CIP, p16, p27, cyclins (D1 and E), cdks (cdk2, cdk4 and cdk6) and PCNA proteins, and the activities of cdks in the SCC-9-p53X cells caused (i) a significant decrease in the cell proliferation, level of the DNA replication protein, PCNA, and anchorage-independent growth, (ii) an inhibition in the activities of cdk2, cdk4, and cdk6 kinases, and(iii) a decrease in the levels of cdk2 and cdk6 proteins. However, dexamethasone failed to induce these changes in the nontransfected SCC-9 cells. These results demonstrate that in human cancer cells containing p53 mutation, the levels of cdk proteins and their kinase activities of the G_1 phase are notably reduced by expression of wt p53 gene thereby making them to repress of tumorigenic phenotype.
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