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CYP17A1 and Androgen-Receptor Expression in Prostate Carcinoma Tissues and Cancer Cell Lines

CYP17A1 and Androgen-Receptor Expression in Prostate Carcinoma Tissues and Cancer Cell Lines Background: CYP17A1 is involved in the steroidogenesis of dehydroepiandrosterone and androstenedione. CYP17A is a target for the hormonal treatment of prostate cancer (PCa). Objectives: To investigate the role of CYP17A1 as a driver of PCa growth. Materials and Methods: We examined the expression of CYP17A1 and of androgen receptors (AR) in PCa specimens and in PCa cell lines. Results: CYP17A1 was strongly expressed in the cytoplasm of PCa cells (median 50% of cancer cells, range 0-100%). The nuclear AR expression in cancer cells was directly related with CYP17A1 (p < 0.0001, r = 0.51). The hormone dependent 22Rv1 cell line expressed the CYP17A1 and AR protein and mRNA, in contrast to the PC3 and DU145 cell lines (p < 0.0001). Testosterone and dexamethasone induced nuclear expression of AR and this effect was abolished by abiraterone. CYP17A1 levels were not affected by the incubation with testosterone, while abiraterone significantly reduced its expression. Abiraterone reduced the growth rate and migration of testosterone stimulated 22Rv1 cells. Conclusions: CYP17A1 is strongly expressed in half about of human prostate carcinomas, implying an intracellular androgen synthesis by cancer cells. Abiraterone effectively blocked nuclear accumulation of AR and suppressed CYP17A1 expression. CYP17A1 may function as a biomarker to select the best hormonal anticancer therapy http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Current Urology Karger

CYP17A1 and Androgen-Receptor Expression in Prostate Carcinoma Tissues and Cancer Cell Lines

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Publisher
Karger
Copyright
© 2019 The Author(s) Published by S. Karger AG, Basel
ISSN
1661-7649
eISSN
1661-7657
DOI
10.1159/000499276
Publisher site
See Article on Publisher Site

Abstract

Background: CYP17A1 is involved in the steroidogenesis of dehydroepiandrosterone and androstenedione. CYP17A is a target for the hormonal treatment of prostate cancer (PCa). Objectives: To investigate the role of CYP17A1 as a driver of PCa growth. Materials and Methods: We examined the expression of CYP17A1 and of androgen receptors (AR) in PCa specimens and in PCa cell lines. Results: CYP17A1 was strongly expressed in the cytoplasm of PCa cells (median 50% of cancer cells, range 0-100%). The nuclear AR expression in cancer cells was directly related with CYP17A1 (p < 0.0001, r = 0.51). The hormone dependent 22Rv1 cell line expressed the CYP17A1 and AR protein and mRNA, in contrast to the PC3 and DU145 cell lines (p < 0.0001). Testosterone and dexamethasone induced nuclear expression of AR and this effect was abolished by abiraterone. CYP17A1 levels were not affected by the incubation with testosterone, while abiraterone significantly reduced its expression. Abiraterone reduced the growth rate and migration of testosterone stimulated 22Rv1 cells. Conclusions: CYP17A1 is strongly expressed in half about of human prostate carcinomas, implying an intracellular androgen synthesis by cancer cells. Abiraterone effectively blocked nuclear accumulation of AR and suppressed CYP17A1 expression. CYP17A1 may function as a biomarker to select the best hormonal anticancer therapy

Journal

Current UrologyKarger

Published: Jan 1, 2019

Keywords: Prostate cancer; CYP17A1; Androgen receptors; Testosterone; Abiraterone

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