Exogenous wild-type p16INK4A gene induces delayed cell proliferation and promotes chemosensitivity through decreased pRB and increased E2F-1 expressions.

International journal of molecular medicine

PubMedID: 12792810

Jeong YW, Kim KS, Oh JY, Park JC, Baek WK, Suh SI, Suh MH, Lee JC, Cho JW. Exogenous wild-type p16INK4A gene induces delayed cell proliferation and promotes chemosensitivity through decreased pRB and increased E2F-1 expressions. Int J Mol Med. 2003;12(1):61-5.
Human gastric cancer SNU 484 cells express mutant p16, which migrates slower than the wild-type p16. We constructed an expression vector containing human p16 cDNA to evaluate the cytotoxic effects of exogenous p16 expression on SNU 484 cell proliferation and to explore the potential use of p16 in cancer gene therapy. The stable transfectant expressing wild-type p16, showed a 2-fold slower growth rate than mock and non-infected cells through down-regulation of CDK4-dependent kinase activity. When cells were transiently transfected with mock or p16 encoded vector, the mock cells showed larger survival colonies than those of wild-type p16. Furthermore, p16-expressing stable transfectant was readily progressed into cell death by combination with treatment of chemotherapeutic drug in a dose-dependent manner. According to western blot analysis, both decreased expression of pRB and increased expression of E2F-1 may contribute to the susceptibility of cell death. Our data indicate that exogenous wild-type p16 induces delayed cell proliferation and promotes chemo-sensitivity in the gastric cancer cell line, implying the promise of p16 in cancer gene therapy.