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Biochem Biophys Res Commun. 2000 Jun 24;273(1):140-6.

NF-kappaB activation is related to the resistance of lung cancer cells to TNF-alpha-induced apoptosis.

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Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, 110-799, Korea.


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.

[Indexed for MEDLINE]

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