Loss of nuclear factor-kappaB is tumor promoting but does not substitute for loss of p53.
Inactivation of apoptotic pathways is a common event in cancer. Two transcription factors that regulate apoptosis during tumorigenesis are p53 and nuclear factor (NF)-kappaB. Although NF-kappaB is generally considered a suppressor of cell death, we showed previously that NF-kappaB can contribute to p53-induced death. Here, we show that loss of p65, a critical subunit of NF-kappaB, can cause resistance to different agents that signal death through p53. Loss of p65 also enhances tumorigenesis induced by E1a and Ras. Unlike loss of p53, however, loss of p65 does not cause anchorage-independent growth or enable tumor development following expression of a single oncogene. These findings reaffirm the role of NF-kappaB in p53-induced death but show that its loss does not substitute for loss of p53 in tumor development. Moreover, this indicates that, although perhaps central to p53 function, loss of the ability to induce programmed cell death does not completely inactivate p53's tumor-suppressive effects.
Ryan
Kevin M
KM
Tumor Cell Death Laboratory, Beatson Institute for Cancer Research, Cancer Research UK Beatson Laboratories, Glasgow, United Kingdom. k.ryan@beatson.gla.ac.uk
O'Prey
Jim
J
Vousden
Karen H
KH
D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000172:deficiency* / Q000502:physiology; D009363:Neoplasm Proteins / Q000172:deficiency / Q000502:physiology; D012190:Retroviridae / Q000235:genetics; D051996:Transcription Factor RelA; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency* / Q000502:physiology; D018631:ras Proteins / Q000235:genetics / Q000502:physiology
D017500:Adenovirus E1A Proteins; D002352:Carrier Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D016159:Tumor Suppressor Protein p53; D018631:ras Proteins