UP-REGULATION OF ENDOGENOUS P53 AND INDUCTION OF IN-VIVO APOPTOSIS INB-LINEAGE LYMPHOMAS OF E-MU-MYC TRANSGENIC MICE BY DEREGULATED C-MYC TRANSGENE

E mu-myc transgenic mice carry a constitutively overexpressed c-myc on cogene and develop B-lineage lymphomas. Previous studies have shown th at c-myc overexpression can lead to in vitro apoptosis. Here, we inves tigated the in vivo effects of altered c-myc expression on cell prolif eration versus death in spontaneously arising E mu-myc tumors. E mu-my c tumors display extensive in vivo apoptosis confined to sma II cluste rs of cells with greatly increased expression of both the c-myc transg ene and the endogenous p53 gene as compared with that in normal, pretu mor, or surrounding tumor tissue. This restricted overexpression of bo th the c-myc transgene and the endogenous p53 gene in small clusters o f apoptotic tumor cells indicates that overexpression of these genes a nd apoptosis are not obligatory or uniform during tumor development an d suggests that further somatic mutations or microenvironmental influe nces may be responsible for these properties. Nevertheless, the clear ability of tumor cells to undergo apoptosis in vivo may be exploitable for therapeutic purposes. (C) 1997 Wiley-Liss, Inc.