the importance of ldl and cholesterol metabolism for prostate epithelial cell growth低密度脂蛋白和胆固醇代谢的重要性对前列腺上皮细胞生长.pdfVIP

The Importance of LDL and Cholesterol Metabolism for Prostate Epithelial Cell Growth 1,2 ¨ ¨ 3 4 ¨ 5 6 4 Teemu J. Murtola *, Heimo Syvala , Pasi Pennanen , Merja Blauer , Tiina Solakivi , Timo Ylikomi , Teuvo L. J. Tammela1,2 1 School of Medicine, University of Tampere, Tampere, Finland, 2 Department of Urology, Tampere University Hospital, Tampere, Finland, 3 Department of Anatomy, School of Medicine, University of Tampere, Tampere, Finland, 4 Department of Cell Biology, School of Medicine, University of Tampere, Tampere, Finland, 5 Department of Gastroenterology and Alimentary Tract Surgery and Tampere Pancreas Laboratory, Tampere University Hospital, Tampere, Finland, 6 Department of Medical Biochemistry, School of Medicine, University of Tampere, Tampere, Finland Abstract Cholesterol-lowering treatment has been suggested to delay progression of prostate cancer by decreasing serum LDL. We studied in vitro the effect of extracellular LDL-cholesterol on the number of prostate epithelial cells and on the expression of key regulators of cholesterol metabolism. Two normal prostatic epithelial cell lines (P96E, P97E), two in vitro immortalized epithelial cell lines (PWR-1E, RWPE-1) and two cancer cell lines (LNCaP and VCaP) were grown in cholesterol-deficient conditions. Cells were treated with 1–50 mg/ml LDL-cholesterol and/or 100 nM simvastatin for seven days. Cell number relative to control was measured with crystal violet staining. Changes in mRNA and protein expression of key effectors in cholesterol metabolism (HMGCR, LDLR, SREBP2 and ABCA1) were measured with RT-PCR and immunoblotting, respectively. LDL increased the relative cell number of prostate cancer cell lines, but reduced the number