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[Cancer Research 62, 2239-2243, April 15, 2002]
© 2002 American Association for Cancer Research

Advances in Brief

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)1

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. Hunt2 and Stephen G. Swisher2,3

Departments of Thoracic and Cardiovascular Surgery [A. P., J. A. R., S. G. S.], and Surgical Oncology [K. K. H., S. A. V.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030; Introgen Therapeutics Inc, Houston, Texas 77030 [S. C., A. M. M., H. Z-Y., A. L. S.]; and Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida 33136 [G. N. B., S. B]

Adenoviral-mediated overexpression of the melanoma differentiation-associated gene 7 (Ad-mda7) induces apoptosis in a wide range of cancer cells, although themechanism is not well understood. We report that Ad-mda7 induces andactivates the double-stranded RNA-dependent protein kinase (PKR), which leads to phosphorylation of the {alpha} subunit of eukaryotic translation initiation factor 2 (eIF-2{alpha}) and the induction of apoptosis in lung cancer cells. Treatment with 2-aminopurine (2-AP), a serine/threonine kinase inhibitor, inhibits PKR activation, eIF2{alpha} 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.




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