Role of cholesterol synthesis and esterification in the growth of CEM and MOLT4 lymphoblastic cells

Abstract

CEM and MOLT4 are human T-cell lines isolated from patients with acute cell leukaemia. In culture they show important differences in cholesterol metabolism, CEM being less efficient at synthesizing cholesterol and having a lower activity of 3-hydroxy-3-methylglutaryl-CoA (HMGCoA) reductase. To investigate further the relationship between regulation of intracellular cholesterol metabolism at various steps and rate of cell growth, cholesterol synthesis, esterification and efflux were evaluated in CEM and MOLT4 cells at different times during exponential and stationary growth in vitro. It was shown that, although CEM cells have a lower rate of cholesterol synthesis, they grow at a faster rate than MOLT4 cells. However, CEM cells exhibit an increased capacity to esterify cholesterol associated with a decreased efflux of newly synthesized cholesterol into the medium. These results provide evidence for an association between the capability to synthesize and retain cell cholesterol esters and the growth rate potential.

Cytotoxic Properties of Clofibrate and other Peroxisome Proliferators: Relevance to Cancer Progression

“…As an example, monoethylhexylphthalate at low or high doses, respectively, exerts anti-and proapoptotic effects on hepatocyte cultures [64]. On this line, data reported on cultured guinea-pig hepatocytes show suppression, no effect, or promotion of apoptosis [99][100][101]. Comparable results have been obtained on human hepatocytes [102,103].…”

Signaling through cholesterol esterification: a new pathway for the cholecystokinin 2 receptor involved in cell growth and invasion

“…Indeed, inhibition of cholesteryl ester formation by inhibiting ACAT reduced by 34% the growth of these cells and by 75% their invasiveness. The increase in cholesterol esterifi cation in these tumor cells was associated with an upregulation of ACAT1 and ACAT2 expression and an increase in ACAT activity as reported for leukemia and renal carcinoma ( 30,32,42 ). The importance of cholesteryl esters in cell proliferation and invasion mediated by an activated CCK2R was also demonstrated in human U87 glioma cells, an autocrine model of activation of the CCK2R ( 20 ).…”

“…Indeed, in cells isolated from patients with lymphoblastic T-cell leukemia, a positive correlation between increased cholesterol esterifi cation and growth rate was associated with higher ACAT mRNA levels, suggesting a link between cholesteryl ester formation and cell proliferation ( 30,42 ). In addition, higher expression and activity of ACAT1 protein in clear cell type renal carcinoma compared with normal kidney tissues have been shown associated with increased levels of cholesteryl ester and with tumor grade ( 32 ).…”

“…Increased production of cholesteryl esters, ACAT expression and activation has been measured in different human tumors compared with normal tissue. In addition, a greater capacity to esterify and accumulate cholesterol in tumor cells has been associated with a higher growth rate, suggesting a link between cholesteryl ester production and cell proliferation (28)(29)(30)(31)(32).…”

Lipoproteins and Cancer

“…Cholesterol esterification and ACAT1 expression were also studied in leukemia cell lines. Cells with a greater ability to esterify cholesterol and with lower cholesterol efflux (CEM) had a higher rate of proliferation as compared to cells with a greater ability to synthesize cholesterol de novo (MOLT4) (Dessi, Batetta et al 1997). Further work demonstrated that the fastergrowing CEM cells expressed more ACAT1 and less HMGCR mRNA as compared to the slower-growing MOLT4 cells (Batetta, Pani et al 1999).…”