PROTOONCOGENES AND GROWTH-FACTORS ASSOCIATED WITH NORMAL AND ABNORMAL LIVER GROWTH

Hepatocyte replication during liver regeneration depends on extrinsic (circulating) and intrinsic (intrahepatic) factors. Two important growth factors produced in the regenerating liver are discussed, TGF-alpha, an autocrine, stimulatory growth factor, and TGF-beta, a paracrine inhibitory factor. The balance between the activities of these factors is likely to play an important role in regulating hepatocyte proliferation. The expression of some protooncogenes occurs sequentially during the first few hours after partial hepatectomy and is a marker for the entry of hepatocytes into the cell cycle (proliferative competence). As hepatocytes become competent to proliferate, they respond to TGF-alpha and other growth factors and enter a proliferative phase. It is possible that TGF-beta-1 serves as a stop signal for liver regeneration but the mechanisms by which TGF-beta inhibits hepatocyte DNA synthesis are still unknown.