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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.

Schörghofer D, Kinslechner K, Preitschopf A, Schütz B, Röhrl C, Hengstschläger M, Stangl H, Mikula M - Reprod. Biol. Endocrinol. (2015)

Bottom Line: Recent data indicate that elevated cholesterol levels in the plasma are a prerequisite for the progression of prostate cancer.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).

View Article: PubMed Central - PubMed

Affiliation: Institute of Medical Genetics, Medical University of Vienna, Währinger Strasse 10, 1090, Vienna, Austria. david.schoerghofer@meduniwien.ac.at.

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.

No MeSH data available.


Related in: MedlinePlus

Correlation of SR-BI with androgen-synthesizing enzymes and the mTOR pathway. Differential expression of HSD17B1 and HSD3B1 in primary tumors (primary site) and metastasizing tumors (metastasis) (a, c, e, g). The arithmetic mean is given as a line within the dots and the P-values of t-test analysis is given within each graph. Scatter plots correlating SR-BI expression with HSD17B1 and HSD3B1 in prostate cancer (b, d, f, h). P-values of Pearson correlation analyses and regression lines are presented within each graph. Red dots represent metastatic and blue dots represent non-metastatic prostate cancer. Analysis of the co-occurrence of SR-BI and ribosomal protein S6 phosphorylation (i–l). A representative high grade prostate cancer is shown with staining for SR-BI (i) and for S6 phosphorylation at serine 240 and 244 in a consecutive area of the same tumor (j). A representative low grade prostate cancer is shown with staining for SR-BI (k) and for S6 phosphorylation at serine 240 and 244 in a consecutive area of the same tumor (l). pS6 = ribosomal protein S6 phosphorylation at serine 240 and 244
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Fig4: Correlation of SR-BI with androgen-synthesizing enzymes and the mTOR pathway. Differential expression of HSD17B1 and HSD3B1 in primary tumors (primary site) and metastasizing tumors (metastasis) (a, c, e, g). The arithmetic mean is given as a line within the dots and the P-values of t-test analysis is given within each graph. Scatter plots correlating SR-BI expression with HSD17B1 and HSD3B1 in prostate cancer (b, d, f, h). P-values of Pearson correlation analyses and regression lines are presented within each graph. Red dots represent metastatic and blue dots represent non-metastatic prostate cancer. Analysis of the co-occurrence of SR-BI and ribosomal protein S6 phosphorylation (i–l). A representative high grade prostate cancer is shown with staining for SR-BI (i) and for S6 phosphorylation at serine 240 and 244 in a consecutive area of the same tumor (j). A representative low grade prostate cancer is shown with staining for SR-BI (k) and for S6 phosphorylation at serine 240 and 244 in a consecutive area of the same tumor (l). pS6 = ribosomal protein S6 phosphorylation at serine 240 and 244

Mentions: Because SR-BI mediates the selective uptake of cholesterol, which can be used for steroidogenesis, we analyzed enzymes that participate in androgen synthesis. We identified the β-hydroxysteroid-dehydrogenases HSD17B1 and HSD17B3 to be significantly up-regulated in metastatic compared to non-metastatic prostate cancer; they also correlated with the intensity of SR-BI expression (Fig. 4a–h).Fig. 4


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

Schörghofer D, Kinslechner K, Preitschopf A, Schütz B, Röhrl C, Hengstschläger M, Stangl H, Mikula M - Reprod. Biol. Endocrinol. (2015)

Correlation of SR-BI with androgen-synthesizing enzymes and the mTOR pathway. Differential expression of HSD17B1 and HSD3B1 in primary tumors (primary site) and metastasizing tumors (metastasis) (a, c, e, g). The arithmetic mean is given as a line within the dots and the P-values of t-test analysis is given within each graph. Scatter plots correlating SR-BI expression with HSD17B1 and HSD3B1 in prostate cancer (b, d, f, h). P-values of Pearson correlation analyses and regression lines are presented within each graph. Red dots represent metastatic and blue dots represent non-metastatic prostate cancer. Analysis of the co-occurrence of SR-BI and ribosomal protein S6 phosphorylation (i–l). A representative high grade prostate cancer is shown with staining for SR-BI (i) and for S6 phosphorylation at serine 240 and 244 in a consecutive area of the same tumor (j). A representative low grade prostate cancer is shown with staining for SR-BI (k) and for S6 phosphorylation at serine 240 and 244 in a consecutive area of the same tumor (l). pS6 = ribosomal protein S6 phosphorylation at serine 240 and 244
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4528807&req=5

Fig4: Correlation of SR-BI with androgen-synthesizing enzymes and the mTOR pathway. Differential expression of HSD17B1 and HSD3B1 in primary tumors (primary site) and metastasizing tumors (metastasis) (a, c, e, g). The arithmetic mean is given as a line within the dots and the P-values of t-test analysis is given within each graph. Scatter plots correlating SR-BI expression with HSD17B1 and HSD3B1 in prostate cancer (b, d, f, h). P-values of Pearson correlation analyses and regression lines are presented within each graph. Red dots represent metastatic and blue dots represent non-metastatic prostate cancer. Analysis of the co-occurrence of SR-BI and ribosomal protein S6 phosphorylation (i–l). A representative high grade prostate cancer is shown with staining for SR-BI (i) and for S6 phosphorylation at serine 240 and 244 in a consecutive area of the same tumor (j). A representative low grade prostate cancer is shown with staining for SR-BI (k) and for S6 phosphorylation at serine 240 and 244 in a consecutive area of the same tumor (l). pS6 = ribosomal protein S6 phosphorylation at serine 240 and 244
Mentions: Because SR-BI mediates the selective uptake of cholesterol, which can be used for steroidogenesis, we analyzed enzymes that participate in androgen synthesis. We identified the β-hydroxysteroid-dehydrogenases HSD17B1 and HSD17B3 to be significantly up-regulated in metastatic compared to non-metastatic prostate cancer; they also correlated with the intensity of SR-BI expression (Fig. 4a–h).Fig. 4

Bottom Line: Recent data indicate that elevated cholesterol levels in the plasma are a prerequisite for the progression of prostate cancer.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).

View Article: PubMed Central - PubMed

Affiliation: Institute of Medical Genetics, Medical University of Vienna, Währinger Strasse 10, 1090, Vienna, Austria. david.schoerghofer@meduniwien.ac.at.

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.

No MeSH data available.


Related in: MedlinePlus