2 MAJOR REGULATORY STEPS IN CHOLESTEROL-SYNTHESIS BY HUMAN RENAL-CANCER CELLS

Two major mechanisms regulating cholesterol biosynthesis exist in a human renal cancer cell line, Caki-1. Caki-1 is a newly established cell line whose characteristics of rapid growth and active cholesterol synthesis qualify it as a potentially valuable tool for elucidation of regulatory mechanism of cholesterol synthesis and transport. In the absence of exogenous cholesterol, cholesterol is the dominant sterol arising from labeled acetate and mevalonate. In the presence of exogenous cholesterol, the conversion of acetate to cholesterol and the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.34) is markedly reduced and this inhibition is released when cholesterol is removed from the medium. The conversion of mevalonate to cholesterol was studied in the presence of exogenous cholesterol. This 2nd major control process results in the accumulation of squalene and may involve additional late steps in cholesterol synthesis or metabolism. The occurrence of 2 major mechanisms regulating cholesterol synthesis may be a property of renal cancer cells or a previously unrecognized characteristic of a variety of cultured cells.