Massive accumulation of neutral lipids in cells conditionally transformed by an activated H-ras oncogene

Phenotypic consequences of ras oncogene expression were studied in cells conditionally transformed by T24 H-ras and a temperature-sensitive SV40 large T antigen (tsA58). Previous studies have demonstrated that transformation of REF52 cells by ras and SV40 large T antigen requires continuous T antigen expression. Thus, tsA58/T24 H-ras transformants ceased growing when transferred to a restrictive temperature for T antigen expression. Inhibition of cell growth was accompanied by massive accumulations of cholesterol esters, triglycerides and a third lipid species, identified as glycerol ethers on the basis of mobility on TLC. Cholesterol esters were derived from serum lipoproteins, and appeared to accumulate because LDL receptor expression and activity did not decline in growth arrested cells. Triglycerides and glycerol ethers were products of cell metabolism. The process lacked features characteristic of adipocyte differentiation, but may suggest mechanisms important in diseases, such as atherosclerosis, that involve abnormal accumulations of neutral lipids. Accumulating lipid species may also include metabolites induced by ras that accumulate in growth-arrested cells.