title: Cholesterol homeostasis in two commonly used human prostate cancer cell-lines, LNCaP and PC-3.
abstract: BACKGROUND
  Recently, there has been renewed interest in the link between cholesterol and prostate cancer. It has been previously reported that in vitro, prostate cancer cells lack sterol-mediated feedback regulation of the major transcription factor in cholesterol homeostasis, sterol-regulatory element binding protein 2 (SREBP-2). This could explain the accumulation of cholesterol observed in clinical prostate cancers. Consequently, perturbed feedback regulation to increased sterol levels has become a pervasive concept in the prostate cancer setting. Here, we aimed to explore this in greater depth.
  
  
  RESULTS
  After altering the cellular cholesterol status in LNCaP and PC-3 prostate cancer cells, we examined SREBP-2 processing, downstream effects on promoter activity and expression of SREBP-2 target genes, and functional activity (low-density lipoprotein uptake, cholesterol synthesis). In doing so, we observed that LNCaP and PC-3 cells were sensitive to increased sterol levels. In contrast, lowering cholesterol levels via statin treatment generated a greater response in LNCaP cells than PC-3 cells. This highlighted an important difference between these cell-lines: basal SREBP-2 activity appeared to be higher in PC-3 cells, reducing sensitivity to decreased cholesterol levels.
  
  
  CONCLUSIONS
  Thus, prostate cancer cells are sensitive to changing sterol levels in vitro, but the extent of this regulation differs between prostate cancer cell-lines. These results shed new light on the regulation of cholesterol metabolism in two commonly used prostate cancer cell-lines, and emphasize the importance of establishing whether or not cholesterol homeostasis is perturbed in prostate cancer in vivo.
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: James Robert
authors.initials: JR
authors.lastname: Krycer
authors.forename: Ika
authors.initials: I
authors.lastname: Kristiana
authors.forename: Andrew John
authors.initials: AJ
authors.lastname: Brown
mesh_terms: D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism* / Q000494:pharmacology; D025461:Feedback, Physiological / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D052138:Genes, Neoplasm / Q000235:genetics; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics / Q000378:metabolism
chemical_list: D011973:Receptors, LDL; D051782:Sterol Regulatory Element Binding Protein 2; D002784:Cholesterol