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Efficient adenoviral transfer of NF‐κB inhibitor sensitizes melanoma to tumor necrosis factor‐mediated apoptosis
Author(s) -
Bakker Talitha R.,
Reed Darryl,
Renno Toufic,
Jongeneel C. Victor
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990118)80:2<320::aid-ijc24>3.0.co;2-k
Subject(s) - tumor necrosis factor alpha , apoptosis , cancer research , cytotoxic t cell , melanoma , cytotoxicity , programmed cell death , necrosis , cell culture , nf κb , biology , adenoviridae , in vitro , immunology , medicine , genetic enhancement , biochemistry , genetics , gene
It has been suggested that the in vitro cytotoxicity of tumor necrosis factor (TNF) toward a number of transformed cell lines could make it a useful agent for anti‐tumor therapy. However, many tumor cell lines are resistant to TNF‐induced cell death. It has been shown that transcription factors of the NF‐κB family, which are themselves activated by TNF, could protect cells against apoptotic cell death. To test whether melanoma cells, which are normally resistant to TNF‐mediated killing, can be made susceptible by inhibiting the activation of NF‐κB, we generated a recombinant adenovirus expressing a dominant mutant form of IκBα under the control of a CMV promoter. We show here that adenovirus‐mediated inhibition of NF‐κB function rendered melanoma cells susceptible to the cytotoxic effects of TNF, and thus that NF‐κB‐inhibiting adenoviruses could become useful adjuvants in TNF‐based anti‐tumor therapies. Int. J. Cancer 80:320–323, 1999. © 1999 Wiley‐Liss, Inc.