REQUIREMENT OF NF-KAPPA-B ACTIVATION TO SUPPRESS P53-INDEPENDENT APOPTOSIS INDUCED BY ONCOGENIC RAS

The ras proto-oncogene is frequently mutated in human tumors and funct ions to chronically stimulate signal transduction cascades resulting i n the synthesis or activation of specific transcription factors, inclu ding Ets, c-Myc, c-Jun, and nuclear factor kappa B (NF-kappa B). These Ras-responsive transcription factors are required for transformation, but the mechanisms by which these proteins facilitate oncogenesis hav e not been fully established. Oncogenic Ras was shown to initiate a p5 3-independent apoptotic response that was suppressed through the activ ation of NF-kappa B. These results provide an explanation for the requ irement of NF-kappa B for Ras-mediated oncogenesis and provide evidenc e that Ras-transformed cells are susceptible to apoptosis even if they do not express the p53 tumor-suppressor gene product.