Requirement of NF-kappaB activation to suppress p53-independent apoptosis induced by oncogenic Ras.
The ras proto-oncogene is frequently mutated in human tumors and functions to chronically stimulate signal transduction cascades resulting in the synthesis or activation of specific transcription factors, including Ets, c-Myc, c-Jun, and nuclear factor kappa B (NF-kappaB). These Ras-responsive transcription factors are required for transformation, but the mechanisms by which these proteins facilitate oncogenesis have not been fully established. Oncogenic Ras was shown to initiate a p53-independent apoptotic response that was suppressed through the activation of NF-kappaB. These results provide an explanation for the requirement of NF-kappaB for Ras-mediated oncogenesis and provide evidence that Ras-transformed cells are susceptible to apoptosis even if they do not express the p53 tumor-suppressor gene product.
Mayo
M W
MW
Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Wang
C Y
CY
Cogswell
P C
PC
Rogers-Graham
K S
KS
Lowe
S W
SW
Der
C J
CJ
Baldwin
A S
AS
D016475:3T3 Cells; D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002461:Cell Line, Transformed; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D011905:Genes, ras; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D051381:Rats; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D017500:Adenovirus E1A Proteins; C000715470:MAS1 protein, human; D016328:NF-kappa B; D000090063:Proto-Oncogene Mas; D016159:Tumor Suppressor Protein p53