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

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 cholester...

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Autores principales: Schörghofer, David, Kinslechner, Katharina, Preitschopf, Andrea, Schütz, Birgit, Röhrl, Clemens, Hengstschläger, Markus, Stangl, Herbert, Mikula, Mario
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528807/
https://www.ncbi.nlm.nih.gov/pubmed/26251134
http://dx.doi.org/10.1186/s12958-015-0087-z
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author Schörghofer, David
Kinslechner, Katharina
Preitschopf, Andrea
Schütz, Birgit
Röhrl, Clemens
Hengstschläger, Markus
Stangl, Herbert
Mikula, Mario
author_facet Schörghofer, David
Kinslechner, Katharina
Preitschopf, Andrea
Schütz, Birgit
Röhrl, Clemens
Hengstschläger, Markus
Stangl, Herbert
Mikula, Mario
author_sort Schörghofer, David
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12958-015-0087-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-45288072015-08-08 The HDL receptor SR-BI is associated with human prostate cancer progression and plays a possible role in establishing androgen independence Schörghofer, David Kinslechner, Katharina Preitschopf, Andrea Schütz, Birgit Röhrl, Clemens Hengstschläger, Markus Stangl, Herbert Mikula, Mario Reprod Biol Endocrinol Research 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12958-015-0087-z) contains supplementary material, which is available to authorized users. BioMed Central 2015-08-07 /pmc/articles/PMC4528807/ /pubmed/26251134 http://dx.doi.org/10.1186/s12958-015-0087-z Text en © Schörghofer et al. 2015 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Schörghofer, David
Kinslechner, Katharina
Preitschopf, Andrea
Schütz, Birgit
Röhrl, Clemens
Hengstschläger, Markus
Stangl, Herbert
Mikula, Mario
The HDL receptor SR-BI is associated with human prostate cancer progression and plays a possible role in establishing androgen independence
title The HDL receptor SR-BI is associated with human prostate cancer progression and plays a possible role in establishing androgen independence
title_full The HDL receptor SR-BI is associated with human prostate cancer progression and plays a possible role in establishing androgen independence
title_fullStr The HDL receptor SR-BI is associated with human prostate cancer progression and plays a possible role in establishing androgen independence
title_full_unstemmed The HDL receptor SR-BI is associated with human prostate cancer progression and plays a possible role in establishing androgen independence
title_short The HDL receptor SR-BI is associated with human prostate cancer progression and plays a possible role in establishing androgen independence
title_sort hdl receptor sr-bi is associated with human prostate cancer progression and plays a possible role in establishing androgen independence
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528807/
https://www.ncbi.nlm.nih.gov/pubmed/26251134
http://dx.doi.org/10.1186/s12958-015-0087-z
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