TY - JOUR
T1 - 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)
AU - Pataer, Abujiang
AU - Vorburger, Stephan A.
AU - Barber, Glen N.
AU - Chada, Sunil
AU - Mhashilkar, Abner M.
AU - Zou-Yang, Helena
AU - Stewart, Alexis L.
AU - Balachandran, Siddharth
AU - Roth, Jack A.
AU - Hunt, Kelly K.
AU - Swisher, Stephen G.
PY - 2002/4/15
Y1 - 2002/4/15
N2 - 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.
AB - 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.
KW - 2-Aminopurine/pharmacology
KW - Adenoviridae/genetics
KW - Apoptosis/genetics
KW - DNA-Binding Proteins/metabolism
KW - Enzyme Induction
KW - Enzyme Inhibitors/pharmacology
KW - Gene Transfer Techniques
KW - Genes, Tumor Suppressor
KW - Growth Substances/genetics
KW - Humans
KW - Interleukins
KW - Lung Neoplasms/enzymology
KW - Phosphorylation
KW - Transcription Factors/metabolism
KW - Tumor Cells, Cultured
KW - Up-Regulation
KW - eIF-2 Kinase/antagonists & inhibitors
UR - http://www.scopus.com/inward/record.url?scp=0037089491&partnerID=8YFLogxK
M3 - Article
C2 - 11956076
AN - SCOPUS:0037089491
SN - 0008-5472
VL - 62
SP - 2239
EP - 2243
JO - Cancer Research
JF - Cancer Research
IS - 8
ER -
