Upregulation of endogenousp53 and induction of in vivo apoptosis in B-lineage lymphomas ofEμ-myc transgenic mice by deregulated c-myc transgene

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Abstract
Eμ‐myc transgenic mice carry a constitutively overexpressed c‐myc oncogene and develop B‐lineage lymphomas. Previous studies have shown that c‐myc overexpression can lead to in vitro apoptosis. Here, we investigated the in vivo effects of altered c‐myc expression on cell proliferation versus death in spontaneously arising Eμ‐myc tumors. Eμ‐myc tumors display extensive in vivo apoptosis confined to small clusters of cells with greatly increased expression of both the c‐myc transgene and the endogenous p53 gene as compared with that in normal, pretumor, or surrounding tumor tissue. This restricted overexpression of both the c‐myc transgene and the endogenous p53 gene in small clusters of apoptotic tumor cells indicates that overexpression of these genes and apoptosis are not obligatory or uniform during tumor development and suggests that further somatic mutations or microenvironmental influences may be responsible for these properties. Nevertheless, the clear ability of tumor cells to undergo apoptosis in vivo may be exploitable for therapeutic purposes. Mol. Carcinog. 18:66–77, 1997.