Evidence for steroidogenic potential in human prostate cell lines and tissues

Bennett, Nigel C., Hooper, John D., Lambie, Duncan, Lee, Cheok S., Yang, Tao, Vesey, David A., Samaratunga, Hemamali, Johnson, David W. and Gobe, Glenda C. (2012) Evidence for steroidogenic potential in human prostate cell lines and tissues. American Journal of Pathology, 181 3: 1078-1087.

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Author Bennett, Nigel C.
Hooper, John D.
Lambie, Duncan
Lee, Cheok S.
Yang, Tao
Vesey, David A.
Samaratunga, Hemamali
Johnson, David W.
Gobe, Glenda C.
Title Evidence for steroidogenic potential in human prostate cell lines and tissues
Journal name American Journal of Pathology  (ERA 2012 Listed)    (ERA 2010 Rank A*)   Check publisher's open access policy
Publication date 2012-09
Sub-type Article
DOI 10.1016/j.ajpath.2012.06.009
Volume number 181
Issue number 3
ISSN 0002-9440; 1525-2191
Start page 1078
End page 1087
Total pages 10
Place of publication New York, United States
Publisher Elsevier
Collection year 2013
Language eng
Abstract Malignant prostate cancer (PCa) is usually treated with androgen deprivation therapies (ADTs). Recurrent PCa is resistant to ADT. This research investigated whether PCa can potentially produce androgens de novo, making them androgen self-sufficient. Steroidogenic enzymes required for androgen synthesis from cholesterol (CYP11A1, CYP17A1, HSD3β, HSD17β3) were investigated in human primary PCa (n = 90), lymph node metastases (LNMs; n = 8), and benign prostatic hyperplasia (BPH; n = 6) with the use of IHC. Six prostate cell lines were investigated for mRNA and protein for steroidogenic enzymes and for endogenous synthesis of testosterone and 5α-dihydrotestosterone. All enzymes were identified in PCa, LNMs, BPH, and cell lines. CYP11A1 (rate-limiting enzyme) was expressed in cancerous and noncancerous prostate glands. CYP11A1, CYP17A1, HSD3β, and HSD17β3 were identified, respectively, in 78%, 52%, 16%, and 82% of human BPH and PCa samples. Approximately 10% of primary PCa, LNMs, and BPH expressed all four enzymes simultaneously. CYP11A1 expression was stable, CYP17A1 increased, and HSD3β and HSD17β3 decreased with disease progression. CYP17A1 expression was significantly correlated with CYP11A1 (P = 0.0009), HSD3β (P = 0.0297), and HSD17β3 (P = 0.0090) in vivo, suggesting CYP17A1 has a key role in prostatic steroidogenesis similar to testis and adrenal roles. In vitro, all cell lines expressed mRNA for all enzymes. Protein was not always detectable; however, all cell lines synthesized androgen from cholesterol. The results indicate that monitoring steroidogenic metabolites in patients with PCa may provide useful information for therapy intervention.
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Document type: Journal Article
Sub-type: Article
Collections: Official 2013 Collection
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Created: Fri, 05 Oct 2012, 12:02:37 EST by David Vesey on behalf of Medicine - Princess Alexandra Hospital