title: The HDL receptor SR-BI is associated with human prostate cancer progression and plays a possible role in establishing androgen independence.
abstract: BACKGROUND
  Human prostate cancer represents one of the most frequently diagnosed cancers in men worldwide. Currently, diagnostic methods are insufficient to identify patients at risk for aggressive prostate cancer, which is essential for early treatment. Recent data indicate that elevated cholesterol levels in the plasma are a prerequisite for the progression of prostate cancer. Here, we analyzed clinical prostate cancer samples for the expression of receptors involved in cellular cholesterol uptake.
  
  
  METHODS
  We screened mRNA microarray files of prostate cancer samples for alterations in the expression levels of cholesterol transporters. Furthermore, we performed immunohistochemistry analysis on human primary prostate cancer tissue sections derived from patients to investigate the correlation of SR-BI with clinicopathological parameters and the mTOR target pS6.
  
  
  RESULTS
  In contrast to LDLR, we identified SR-BI mRNA and protein expression to be induced in high Gleason grade primary prostate cancers. Histologic analysis of prostate biopsies revealed that 53.6 % of all cancer samples and none of the non-cancer samples showed high SR-BI staining intensity. The disease-free survival time was reduced (P = 0.02) in patients expressing high intra-tumor levels of SR-BI. SR-BI mRNA correlated with HSD17B1 and HSD3B1 and SR-BI protein staining showed correlation with active ribosomal protein S6 (RS = 0.828, P < 0.00001).
  
  
  CONCLUSIONS
  We identified SR-BI to indicate human prostate cancer formation, suggesting that increased levels of SR-BI may be involved in the generation of a castration-resistant phenotype.
authors.affiliation: Institute of Medical Genetics, Medical University of Vienna, Währinger Strasse 10, 1090, Vienna, Austria. david.schoerghofer@meduniwien.ac.at.
authors.forename: David
authors.initials: D
authors.lastname: Schörghofer
authors.affiliation: Institute of Medical Genetics, Medical University of Vienna, Währinger Strasse 10, 1090, Vienna, Austria. katharina.kinslechner@meduniwien.ac.at.
authors.forename: Katharina
authors.initials: K
authors.lastname: Kinslechner
authors.affiliation: Institute of Medical Genetics, Medical University of Vienna, Währinger Strasse 10, 1090, Vienna, Austria. andrea.preitschopf@meduniwien.ac.at.
authors.forename: Andrea
authors.initials: A
authors.lastname: Preitschopf
authors.affiliation: Institute of Medical Genetics, Medical University of Vienna, Währinger Strasse 10, 1090, Vienna, Austria. birgit.schuetz@meduniwien.ac.at.
authors.forename: Birgit
authors.initials: B
authors.lastname: Schütz
authors.affiliation: Institute of Medical Chemistry, Medical University of Vienna, Währinger Strasse 10, 1090, Vienna, Austria. clemens.roehrl@meduniwien.ac.at.
authors.forename: Clemens
authors.initials: C
authors.lastname: Röhrl
authors.affiliation: Institute of Medical Genetics, Medical University of Vienna, Währinger Strasse 10, 1090, Vienna, Austria. markus.hengstschlaeger@meduniwien.ac.at.
authors.forename: Markus
authors.initials: M
authors.lastname: Hengstschläger
authors.affiliation: Institute of Medical Chemistry, Medical University of Vienna, Währinger Strasse 10, 1090, Vienna, Austria. herbert.stangl@meduniwien.ac.at.
authors.forename: Herbert
authors.initials: H
authors.lastname: Stangl
authors.affiliation: Institute of Medical Genetics, Medical University of Vienna, Währinger Strasse 10, 1090, Vienna, Austria. mario.mikula@meduniwien.ac.at.
authors.forename: Mario
authors.initials: M
authors.lastname: Mikula
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D018955:CD36 Antigens