The HDL receptor SR-BI is associated with human prostate cancer progression and plays a possible role in establishing androgen independence

David Schörghofer, Katharina Kinslechner, Andrea Preitschopf, Birgit Schütz, Clemens Röhrl, Markus Hengstschläger, Herbert Stangl, Mario Mikula

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)

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.

Original languageEnglish
Article number88
Pages (from-to)88
JournalReproductive Biology and Endocrinology
Volume13
Issue number1
DOIs
Publication statusPublished - 7 Aug 2015
Externally publishedYes

Keywords

  • Androgen synthesis
  • Cholesterol
  • LDLR
  • mTOR
  • SCARB1
  • CD36 Antigens/genetics
  • Prostatic Neoplasms/genetics
  • Humans
  • Male
  • Prostate/metabolism
  • Disease Progression
  • Disease-Free Survival
  • Neoplasm Grading
  • Adenocarcinoma/genetics

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