Altered low density lipoprotein receptor regulation is associated with cholesteryl ester accumulation in Simian virus 40 transformed rodent fibroblast cell lines.

Abstract

Several SV40 transformed REF52 cell lines were found to accumulate 5 to 10 times more cholesteryl esters compared to their parent line REF52 when cultured in 10% serum. Under this culture condition, the cholesteryl ester to phospholipid ratio was 0.4:1 and 2.0:1 to 3.8:1 for normal and SV40 transformed cells, respectively. The mechanism underlying cholesteryl ester accumulation in SV40 transformed lines was investigated. We found that 1) the rate of the de novo cholesterol and cholesteryl ester synthesis was roughly equal in normal and transformed derivatives; 2) the accumulation of cholesteryl esters in the transformants would not occur when cultured in lipoprotein-deficient medium and reappeared upon their return to low density lipoprotein-containing medium; 3) the transformants expressed twice as many low density lipoprotein receptors and were less sensitive to LDL-induced receptor down regulation compared to their nontransformed counterparts. The results indicate that SV40 transformed lines exhibited an accelerated lipid uptake from the culture medium due to an altered regulation of low density lipoprotein receptor activity.