NF-kappaB activation is related to the resistance of lung cancer cells to TNF-alpha-induced apoptosis.
In diverse cell types, NF-kappaB transcription factors have been shown to have a role in regulating the apoptotic program, either as essential for the induction of apoptosis or, perhaps more commonly, as blockers of apoptosis. We investigated the role of NF-kappaB activation in the TNF-alpha-mediated apoptosis in lung cancer cells. TNF-alpha-resistant NCI-H157 cells became sensitized to TNF-alpha by prior treatment with cycloheximide, suggesting the presence of newly synthesized antiapoptotic protein(s). We next evaluated whether the transcription of antiapoptotic protein(s) depends on the activation of NF-kappaB. NF-kappaB activation was blocked by either adenovirus-mediated overexpression of IkappaBalpha superrepressor or pretreatment with proteasome inhibitor, MG132. Both methods of blocking NF-kappaB activation enhanced TNF-alpha-induced apoptosis in NCI-H157 cells. These results suggest that NF-kappaB activation confers resistance to TNF-alpha-mediated apoptosis in lung cancer cells.
Kim
J Y
JY
Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, 110-799, Korea.
Lee
S
S
Hwangbo
B
B
Lee
C T
CT
Kim
Y W
YW
Han
S K
SK
Shim
Y S
YS
Yoo
C G
CG
D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects*; D003513:Cycloheximide / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D020672:I-kappa B Proteins; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009097:Multienzyme Complexes / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D046988:Proteasome Endopeptidase Complex; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D020672:I-kappa B Proteins; D009097:Multienzyme Complexes; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D009363:Neoplasm Proteins; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D003513:Cycloheximide; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex