Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1782384708812800000 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4528807 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT schorghoferdavid thehdlreceptorsrbiisassociatedwithhumanprostatecancerprogressionandplaysapossibleroleinestablishingandrogenindependence AT kinslechnerkatharina thehdlreceptorsrbiisassociatedwithhumanprostatecancerprogressionandplaysapossibleroleinestablishingandrogenindependence AT preitschopfandrea thehdlreceptorsrbiisassociatedwithhumanprostatecancerprogressionandplaysapossibleroleinestablishingandrogenindependence AT schutzbirgit thehdlreceptorsrbiisassociatedwithhumanprostatecancerprogressionandplaysapossibleroleinestablishingandrogenindependence AT rohrlclemens thehdlreceptorsrbiisassociatedwithhumanprostatecancerprogressionandplaysapossibleroleinestablishingandrogenindependence AT hengstschlagermarkus thehdlreceptorsrbiisassociatedwithhumanprostatecancerprogressionandplaysapossibleroleinestablishingandrogenindependence AT stanglherbert thehdlreceptorsrbiisassociatedwithhumanprostatecancerprogressionandplaysapossibleroleinestablishingandrogenindependence AT mikulamario thehdlreceptorsrbiisassociatedwithhumanprostatecancerprogressionandplaysapossibleroleinestablishingandrogenindependence AT schorghoferdavid hdlreceptorsrbiisassociatedwithhumanprostatecancerprogressionandplaysapossibleroleinestablishingandrogenindependence AT kinslechnerkatharina hdlreceptorsrbiisassociatedwithhumanprostatecancerprogressionandplaysapossibleroleinestablishingandrogenindependence AT preitschopfandrea hdlreceptorsrbiisassociatedwithhumanprostatecancerprogressionandplaysapossibleroleinestablishingandrogenindependence AT schutzbirgit hdlreceptorsrbiisassociatedwithhumanprostatecancerprogressionandplaysapossibleroleinestablishingandrogenindependence AT rohrlclemens hdlreceptorsrbiisassociatedwithhumanprostatecancerprogressionandplaysapossibleroleinestablishingandrogenindependence AT hengstschlagermarkus hdlreceptorsrbiisassociatedwithhumanprostatecancerprogressionandplaysapossibleroleinestablishingandrogenindependence AT stanglherbert hdlreceptorsrbiisassociatedwithhumanprostatecancerprogressionandplaysapossibleroleinestablishingandrogenindependence AT mikulamario hdlreceptorsrbiisassociatedwithhumanprostatecancerprogressionandplaysapossibleroleinestablishingandrogenindependence |