Correlation between cholesterol esterification, MDR1 gene expression and rate of cell proliferation in CEM and MOLT4 cell lines

A positive correlation between cholesterol esterification and growth rate p otential was previously found in our laboratory during the growth of CEM an d MOLT4 lymphoblastic cells. In the current study, we investigated whether the rates of cholesterol esters synthesis correlate with changes of acyl-Co Acholesterol acyltransferase (ACAT) mRNA levels and of other genes implied in cholesterol biosynthesis and uptake? such as 3-hydroxy-3-methylglutaryl- CoA (HMGCoA) reductase and low density lipoprotein (LDL) receptor. The resu lts showed that the more rapid growing CEM cells had lower levels of expres sion of HMGCoA-reductase and LDL receptors compared to MOLT4. By contrast, ACAT mRNA levels were higher in CEM cells, further supporting the concept o f a possible involvement of cholesterol esters in the regulation of cell gr owth and division. In this study, high levels of cholesterol esterification and of expression of ACAT gene were also associated with a markedly increa sed expression of multidrug resistance (MDR1) gene, suggesting that MDR1 ac tivity might contribute to regulate the fate of cell growth and division by modulating intracellular cholesterol ester levels.