The importance of LDL and cholesterol metabolism for prostate epithelial cell growth

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dc.contributor.author Murtola, Teemu
dc.contributor.author Syvälä, Heimo
dc.contributor.author Pennanen, Pasi
dc.contributor.author Bläuer, Merja
dc.contributor.author Solakivi, Tiina
dc.contributor.author Ylikomi, Timo
dc.contributor.author Tammela, Teuvo
dc.date.accessioned 2012-08-22T08:13:32Z
dc.date.available 2012-08-22T08:13:32Z
dc.date.issued 2012
dc.identifier.issn 1932-6203 -
dc.identifier.uri http://tampub.uta.fi/handle/10024/66318
dc.description Public Library of Science open access -
dc.description.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 µg/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 of normal epithelial cells at high concentrations. Treatment with cholesterol-lowering simvastatin induced up to 90% reduction in relative cell number of normal cell lines but a 15–20% reduction in relative number of cancer cells, an effect accompanied by sharp upregulation of HMGCR and LDLR. These effects were prevented by LDL. Compared to the normal cells, prostate cancer cells showed high expression of cholesterol-producing HMGCR but failed to express the major cholesterol exporter ABCA1. LDL increased relative cell number of cancer cell lines, and these cells were less vulnerable than normal cells to cholesterol-lowering simvastatin treatment. Our study supports the importance of LDL for prostate cancer cells, and suggests that cholesterol metabolism in prostate cancer has been reprogrammed to increased production in order to support rapid cell growth. -
dc.language.iso en -
dc.title The importance of LDL and cholesterol metabolism for prostate epithelial cell growth -
dc.type fi=Artikkeli aikakauslehdessä | en=Journal Article| -
dc.identifier.urn URN:NBN:fi:uta-201208221029 -
dc.identifier.doi doi:10.1371/journal.pone.0039445 -
dc.type.version fi=Kustantajan versio | en=Publisher's version| -
dc.administrativeunit fi=Lääketieteen yksikkö | en=School of Medicine| -
dc.journal.title Plos ONE -
dc.journal.volume 7 -
dc.journal.number 6 -
dc.journal.volumepagerange 1-8 -
dc.journal.url http://dx.doi.org/10.1371/journal.pone.0039445 -

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