Adenoviral transfer of the melanoma differentiation-associated gene 7 (mda7) induces apoptosis of lung cancer cells via up-regulation of the double-stranded RNA-dependent protein kinase (PKR)

Abujiang Pataer, Stephan A. Vorburger, Glen N. Barber, Sunil Chada, Abner M. Mhashilkar, Helena Zou-Yang, Alexis L. Stewart, Siddharth Balachandran, Jack A. Roth, Kelly K. Hunt, Stephen G. Swisher

Research output: Contribution to journalArticlepeer-review

133 Scopus citations

Abstract

Adenoviral-mediated overexpression of the melanoma differentiation-associated gene 7 (Ad-mda7) induces apoptosis in a wide range of cancer cells, although the mechanism is not well understood. We report that Ad-mda7 induces and activates the double-stranded RNA-dependent protein kinase (PKR), which leads to phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF-2α) and the induction of apoptosis in lung cancer cells. Treatment with 2-aminopurine (2-AP), a serine/threonine kinase inhibitor, inhibits PKR activation, eIF2α phosphorylation, and apoptosis induction by Ad-mda7. Additionally, PKR null but not wild-type fibroblasts are resistant to Ad-mda7-induced apoptosis. These results suggest that the activation of PKR and its downstream targets may be a critical pathway for Ad-mda7-mediated apoptosis.

Original languageEnglish (US)
Pages (from-to)2239-2243
Number of pages5
JournalCancer Research
Volume62
Issue number8
StatePublished - Apr 15 2002

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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