Reduced rates of proteolysis in transformed cells

Abstract

GROWTH of cells implies a net accumulation of intracellular proteins with the rate of protein synthesis exceeding the rate of protein degradation. It follows that the seemingly uncontrolled growth of transformed cells could be produced by a reduction in intracellular proteolysis without any concomitant increase in protein synthesis. In order to examine this hypothesis we have determined the rates of protein degradation in two pairs of (non-isogenic) cell types—non-growing rat liver hepatocytes and the chemically transformed Reuber H35 hepatoma, and mouse BALB/c 3T3 fibroblasts and 3T3 fibroblasts transformed with Simian Virus 40 (SV40). We have measured proteolysis over a wide range of insulin concentrations with cells incubated in either an enriched medium or a basal salts medium (step-down conditions). Insulin was chosen because it inhibits intracellular proteolysis in several cell types^1–6 and may have a major role in the normal regulation of proteolysis in vivo. We report here that transformed cells have a lower basal rate of proteolysis together with an increased sensitivity towards inhibition by insulin, two factors which will contribute to the rapid growth of such cells.