Induction of ribosomal genes and hepatocyte hypertrophy by adenovirus-mediated expression of c-Myc <i>in vivo</i>

Abstract

Overexpression of c-Myc in immortalized cells increases cell proliferation, inhibits cell differentiation, and promotes cell transformation. Recent evidence suggests that these effects, however, do not necessarily occur when c-Myc is overexpressed in primary mammalian cells. We sought to determine the immediate effects of transient overexpression of c-Myc in primary cells in vivo by using recombinant adenovirus to overexpress human MYC in mouse liver. Mice were intravenously injected with adenoviruses encoding MYC (Ad/Myc), E2F-1 (Ad/E2F-1), or beta-galactosidase (Ad/LacZ). Transgene expression was detectable 4 days after injection. Expression of ectopic c-Myc was immediately accompanied by enlarged and dysmorphic hepatocytes in the absence of significant cell proliferation or apoptosis. These findings were not present in the livers of mice injected with Ad/E2F-1 or Ad/LacZ. Prominent hepatocyte nuclei and nucleoli were associated with the up-regulation of large- and small-subunit ribosomal and nucleolar genes, suggesting that c-Myc may induce their expression to increase cell mass. Our studies support a role for c-Myc in the in vivo control of vertebrate cell size and metabolism independent of cell proliferation.