Adenovirus-mediated p53 gene transduction inhibits telomerase activity independent of its effects on cell cycle arrest and apoptosis in human pancreatic cancer cells

Evidence for a relationship between overexpression of wild-type p53 and tel omerase activity remains controversial, We investigated whether p53 gene tr ansduction could cause telomerase inhibition in pancreatic cancer cell line s, focusing on the relation of transduction to growth arrest, cell cycle ar rest, and apoptotic cell death. The cells were infected with recombinant ad enovirus expressing wild-type p53 or p21(WAF1) at a multiplicity of infecti on of 100 or were continuously er;posed to 10 mu M VP-16, which is well kno wn to induce apoptosis, Adenovirus-mediated p53 gene transduction caused G( 1) cell cycle arrest, apoptosis, and resultant growth inhibition in MIA PaC a-2 cells; the cell number 2 days after infection was 50% of preinfection v alue, and 13% of the cells were dead. Moreover, the transduction resulted i n complete depression of telomerase activity through downregulation of hTER T mRNA expression. In contrast, p21(WAF1) gene transduction only arrested c ell growth and cell cycle at G(1) phase, and VP-16 treatment inhibited cell growth with G(2)-M arrest and apoptosis; after treatment, the cell number was 73% of pretreatment, and 12% of the cells were dead. Neither p21(WAF1) gene transduction nor VP-16 treatment caused telomerase inhibition. Similar results were obtained in two other pancreatic cancer cell lines, SUIT-2 an d AsPC-1, Thus, our results demonstrate that the p53 gene transduction dire ctly inhibits telomerase activity, independent of its effects on cell growt h arrest, cell cycle arrest, and apoptosis.