Acinar cell carcinoma of rat pancreas: mechanism of deregulation of cholesterol metabolism.

The mechanism of deregulation of cholesterol metabolism was studied in fast and slow growing nude mouse tumors and cancer cells in culture derived from azaserine-induced rat pancreatic acinar cell carcinoma. The tumors showed a loss of feedback control of the de novo synthesis of cholesterol, probably due to a loss of low density lipoprotein (LDL) receptors on plasma membranes or to a defect in the binding and internalization of LDL in the cancer cells. The hexosemonophosphate shunt pathway is stimulated in the cancer cells, presumably because of an increased demand for NADPH in cholesterol synthesis and for ribose phosphate in DNA synthesis. The uncontrolled de novo synthesis of cholesterol is one of the factors responsible for the high rate of cell proliferation in the tumors.