HEPATOCYTE PROLIFERATION IN STEPWISE DEVELOPMENT OF EXPERIMENTAL LIVER-CELL CANCER

Cell proliferation is the most central and key phenotypic property of cancer including hepatocellular carcinoma. Hepatocyte proliferation is central not only at the late steps in carcinogenesis, the cancer, but at the earliest known step, initiation. Compensatory or regenerative hepatocyte proliferation is essential to initiation with chemical carcinogens but primary hyperplasia is ineffective. During promotion, hepatocyte proliferation is the major change seen as clonal proliferation to generate nodules occurs. During progression, autonomous hepatocyte proliferation balanced by cell loss makes its appearance. This continues in a balanced fashion with only a slight excess of proliferation over loss until the earlier steps in malignancy at which time the balance is disrupted.