E1A oncogene-induced cellular sensitization to immune-mediated apoptosis is independent of p53 and resistant to blockade by E1B 19 kDa protein

E1A oncogene expression sensitizes mammalian cells to apoptosis triggered b y cytolytic lymphocytes (CL) [16]. Most studies suggest that E1A-induced ap optosis involves a p53-dependent cellular pathway that is blocked by the E1 B 19 kDa gene product. In this study, the roles of p53 and E1B 19 kDa were tested for E1A sensitization to CL-induced apoptosis in contrast with apopt osis triggered by TNF alpha or chemical injuries. E1A sensitization to immu ne-mediated (CL- or TNF-induced) apoptosis was independent of p53 expressio n and was resistant to blockade by E1B 19 kDa protein in mouse and hamster cells. In contrast, the p53 requirement for chemically induced apoptosis of E1A-sensitized cells varied with the agent used to treat cells. Apoptosis induced by diverse chemical agents (hygromycin, beauvericin, etoposide, H2O 2) was blocked by E1B 19 kDa expression. Therefore, both the p53-dependence and the E1B 19 kDa blockade of E1A-induced cellular sensitization to apopt otic injury depend on the type of proapoptotic injury tested. These data su ggest that the mechanisms by which E1A sensitizes tumor cells to immune-med iated apoptosis and to rejection by immunocompetent animals do not require cellular expression of wild-type p53 and can function independently of the Bcl-2-like, antiapoptotic mechanisms of E1B 19 kDa. (C) 1999 Academic Press .