Adenoviral Bak overexpression mediates caspase-dependent tumor killing.
One of the most promising strategies in cancer gene therapy is adenoviral transfer of proapoptotic genes. We therefore evaluated the novel strategy of adenovirally overexpressing the proapoptotic Bak gene. Our results showed marked apoptosis in cancer cells in vivo and in vitro after Bak gene transfer via a binary adenoviral vector system. This effect was not seen in a caspase 3-defective cell line (MCF-7) and was abrogated in Bak-sensitive tumors after administration of the caspase inhibitor z-DEVD-fmk. Our results suggest that adenoviral-mediated overexpression of Bak provides a novel therapeutic strategy for cancer therapy, but this process appears to be caspase dependent.
Pataer
A
A
Department of Thoracic and Cardiovascular Surgery, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Fang
B
B
Yu
R
R
Kagawa
S
S
Hunt
K K
KK
McDonnell
T J
TJ
Roth
J A
JA
Swisher
S G
SG
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000502:physiology*; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000628:therapy*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D014407:Tumor Cells, Cultured; D050998:bcl-2 Homologous Antagonist-Killer Protein
C494772:BAK1 protein, human; C494773:Bak1 protein, mouse; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D020169:Caspases