Effect of Bcl-2 expression on hepatic preneoplasia in mice.

In a transgenic model of hepatocellular carcinoma induced by the expression of SV40 early sequences (TAg mice), deregulation of hepatocyte proliferation induces an apoptotic process whose decrease coincides with the appearance of neoplastic foci. Mating these mice with transgenic mice overexpressing Bcl-2 led to a dramatic reduction in the number of apoptotic hepatocytes during preneoplasia, resulting in an enlargement of the liver. This decrease in apoptosis was followed, 2 weeks later, by a reduction in hepatocellular proliferation. Sequential reduction in apoptosis and proliferation rate suggests that the anti-apoptotic and the anti-mitotic activities of Bcl-2 might be operative in distinct stages of preneoplasia.