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

Masahiro Kusumoto, Takahiro Ogawa, Kazuhiro Mizumoto, Hikaru Ueno, Hideaki Niiyama, Norihiro Sato, Masafumi Nakamura, Masao Tanaka

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Evidence for a relationship between overexpression of wild-type p53 and telomerase activity remains controversial. We investigated whether p53 gene transduction could cause telomerase inhibition in pancreatic cancer cell lines, focusing on the relation of transduction to growth arrest, cell cycle arrest, and apoptotic cell death. The cells were infected with recombinant adenovirus expressing wild-type p53 or p21(WAF1) at a multiplicity of infection of 100 or were continuously exposed to 10 μM VP-16, which is well known to induce apoptosis. Adenovirus-mediated p53 gene transduction caused G1 cell cycle arrest, apoptosis, and resultant growth inhibition in MIA PaCa-2 cells; the cell number 2 days after infection was 50% of preinfection value, and 13% of the cells were dead. Moreover, the transduction resulted in complete depression of telomerase activity through down-regulation of hTERT mRNA expression. In contrast, p21(WAF1) gene transduction only arrested cell growth and cell cycle at G1 phase, and VP-16 treatment inhibited cell growth with G2-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 and AsPC-1. Thus, our results demonstrate that the p53 gene transduction directly inhibits telomerase activity, independent of its effects on cell growth arrest, cell cycle arrest, and apoptosis.

Original languageEnglish
Pages (from-to)2140-2147
Number of pages8
JournalClinical Cancer Research
Volume5
Issue number8
Publication statusPublished - Aug 1 1999

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this