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. 2003 Jan 28;32(1):49–61. doi: 10.1046/j.1365-2184.1999.3210049.x

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

B Batetta 1, A Pani 2, M Putzolu 1, F Sanna 1, R Bonatesta 1, S Piras 1, O Spano 1, M F Mulas 1, S Dessí 1
PMCID: PMC6726313  PMID: 10371303

Abstract

Abstract. A positive correlation between cholesterol esterification and growth rate potential was previously found in our laboratory during the growth of CEM and MOLT4 lymphoblastic cells. In the current study, we investigated whether the rates of cholesterol esters synthesis correlate with changes of acyl‐CoAcholesterol 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 results showed that the more rapid growing CEM cells had lower levels of expression of HMGCoA‐reductase and LDL receptors compared to MOLT4. By contrast, ACAT mRNA levels were higher in CEM cells, further supporting the concept of a possible involvement of cholesterol esters in the regulation of cell growth and division. In this study, high levels of cholesterol esterification and of expression of ACAT gene were also associated with a markedly increased expression of multidrug resistance (MDR1) gene, suggesting that MDR1 activity might contribute to regulate the rate of cell growth and division by modulating intracellular cholesterol ester levels.

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REFERENCES

  1. Bellamy WT. (1996) P‐glycoproteins and multidrug resistance. Annu. Rev. Pharmacol. Toxicol. 36, 161. [DOI] [PubMed] [Google Scholar]
  2. Brown MS, Goldstein JL. (1979) Receptor‐mediated endocytosis: insights form the lipoprotein receptor system. Proceedings Natl. Acad. Sci. U.S.a 76, 3330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Butke TM, Folks TM. (1992) Complete replacement of membrane cholesterol with 4,4′‐14‐trimethyl sterols in a human T cell line defective in lanosterol demethylation. J. Biol. Chem. 267, 8819. [PubMed] [Google Scholar]
  4. Chomczynsky P, Sacchi N. (1987) Single‐step method of RNA isolation by acid guanidium thiocyanate‐phenol‐chloroform extraction. Anal. Biochem. 162, 156. [DOI] [PubMed] [Google Scholar]
  5. Debry P, Nash EA, Neklason DW, Metherall E. (1997) Role of multidrug resistance P‐glycoproteins in cholesterol esterification. J. Biol. Chem. 272, 1026. [DOI] [PubMed] [Google Scholar]
  6. Dessi S, Batetta B, Anchisi C et al. (1992a) Cholesterol metabolism during the growth of a rat ascites hepatoma (Yoshida AH‐130). Br. J. Cancer 66, 787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dessi S, Batetta B, Laconi E, Ennas C, Pani P. (1984) Hepatic cholesterol in lead nitrate induced liver hyperplasia. Chem. Biol. Interact. 48, 271. [DOI] [PubMed] [Google Scholar]
  8. Dessi S, Batetta B, Pani A et al. (1997) Role of cholesterol synthesis and esterification in the growth of CEM and MOLT4 lymphoblastic cells. Biochem. J. 321, 603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dessi S, Batetta B, Pulisci D, Accogli P, Broccia G, Pani P. (1991) Total and HDL cholesterol in human hematologic neoplasms. Int. J. Hematol. 54, 483. [PubMed] [Google Scholar]
  10. Dessi S, Batetta B, Pulisci D et al. (1994) Cholesterol content in tumor tissues is inversely associated with HDL‐cholesterol in serum in patients with gastrointestinal cancer. Cancer 73, 253. [DOI] [PubMed] [Google Scholar]
  11. Dessi S, Batetta B, Pulisci D et al. (1992b) Altered pattern of lipid metabolism in patients with lung cancer. Oncology 49, 436. [DOI] [PubMed] [Google Scholar]
  12. Dessi S, Batetta B, Spano O et al. (1990) Serum lipoproteins during bone marrow hyperplasia after phenylhydrazine administration in rats. Int. J. Exp. Pathol. 71, 671. [PMC free article] [PubMed] [Google Scholar]
  13. Dessi S, Chiodino C, Batetta B, Fadda AM, Anchisi C, Pani P. (1986) Hepatic glucose‐6‐phosphate dehydrogenase, cholesterogenesis and serum lipoproteins in liver regeneration after partial hepatectomy. Exp. Mol. Pathol. 44, 169. [DOI] [PubMed] [Google Scholar]
  14. Field FJ, Born E, Chen H, Murthy S, Mathur SN. (1995) Esterification of plasma membrane cholesterol and triacyglycerol‐rich lipoprotein secretion in CaCo‐2 cells: possible role of p‐glycoprotein. J. Lipid Res. 36, 1533. [PubMed] [Google Scholar]
  15. Gebhard RL, Clayman RV, Prigge WF et al. (1987) Abnormal cholesterol metabolism in renal clear cell carcinoma. J. Lipid Res. 28, 1177. [PubMed] [Google Scholar]
  16. Harwood HJ, Alvarez IM, Noyes WD, Stacpoole PW. (1991) In vivo regulation of human leukocyte 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase: increased enzyme protein concentration and catalytic efficiency in human leukemia and lymphoma. J. Lipid Res. 32, 1237. [PubMed] [Google Scholar]
  17. Lange Y, Steck TL. (1994) Cholesterol homeostasis‐modulation by amphiphiles. J. Biol. Chem. 269, 29371. [PubMed] [Google Scholar]
  18. Lange Y, Steck TL. (1997) Quantitation of the pool of cholesterol associated with acyl‐CoA: cholesterol acyltransferase in human fibroblasts. J. Biol. Chem. 272, 13103. [DOI] [PubMed] [Google Scholar]
  19. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. (1951) Protein measurement with Folin phenol reagent. J. Biol. Chem. 193, 265. [PubMed] [Google Scholar]
  20. Metherall JE, Li H, Waugh K. (1996a) Role of multidrug resistance P‐glycoproteins in cholesterol biosynthesis. J. Biol. Chem. 271, 2634. [DOI] [PubMed] [Google Scholar]
  21. Metherall JE, Waugh K, Huijuan L. (1996b) Progesterone inhibits cholesterol biosynthesis in cultured cells. J. Biol. Chem. 271, 2627. [DOI] [PubMed] [Google Scholar]
  22. Noonan KE, Beck C, Holzmayer TA et al. (1990) Quantitative analysis of MDR1 (multidrug resistance) gene expression in human tumors by polymerase chain reaction. Proc. Natl. Acad. Sci. 87, 7160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Oppenheimer MJ, Oram JF, Birman L. (1987) Down‐regulation of high density lipoprotein receptor activity of cultured fibroblasts by platelet‐derived growth factor. Arteriosclerosis 7, 325. [DOI] [PubMed] [Google Scholar]
  24. Ross R. (1986) The pathogenesis of atherosclerosis—an update Ross, R. (1986). N. Engl. J. Med. 314, 488. [DOI] [PubMed] [Google Scholar]
  25. Suckling KE, Stange EF. (1985) Role of acyl‐CoA: cholesterol acyltransferase in cellular cholesterol metabolism. J. Lipid Res. 26, 647. [PubMed] [Google Scholar]

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