Abstract | BACKGROUND: METHODS: LNCaP cells were treated with T and/or PRL. CPD expression was measured. Regulation by T (low doses) was determined using transfected cells overexpressing 5α-reductase type-1 (5αR1), which converts T to the more potent dihydrotestosterone. The effects of siRNAs targeting CPD (siCPDs) on NO production, cell viability, and apoptosis were determined using DAF2-DA, MTS, and Annexin-V assays. The effects of PRL/T on CPD/NO levels in PC-3, MDA-PCa-2b, and 22Rv1 cells were also evaluated. RESULTS: In LNCaP cells, 10 nM T and 10 ng/ml PRL-upregulated CPD mRNA/ protein levels. In pTRE-transfectants, 1 nM T-upregulated CPD mRNA levels by ∼2-fold over controls, whereas 0.1 nM T caused similar upregulation in pTRE-5αR1-transfectants. In LNCaP cells cultured in arginine-free medium, addition of furylacryloyl-Ala-Arg (FAR; CPD substrate) increased NO levels. NO production, with FAR, was enhanced by PRL and/or T. siCPDs decreased NO production and cell viability, but increased apoptosis. QPCR analysis showed T/PRL-upregulation of CPD in 22Rv1, MDA-PCa-2b, and PC-3 cells. NO production was doubled by T/PRL in 22Rv1 cells, tripled by T in MDA-PCa-2b cells, and marginally increased by PRL in MDA-PCa-2b and PC-3 cells. CONCLUSIONS: T and PRL upregulate CPD and NO levels in PCa cells. CPD increases NO production to promote PCa cell survival.
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Authors | Lynn N Thomas, Timothy J Morehouse, Catherine K L Too |
Journal | The Prostate
(Prostate)
Vol. 72
Issue 4
Pg. 450-60
(Mar 2012)
ISSN: 1097-0045 [Electronic] United States |
PMID | 21688280
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2011 Wiley Periodicals, Inc. |
Chemical References |
- RNA, Small Interfering
- Nitric Oxide
- Testosterone
- Prolactin
- Arginine
- Carboxypeptidases
- carboxypeptidase D
|
Topics |
- Adenocarcinoma
(metabolism, pathology)
- Apoptosis
(drug effects)
- Arginine
(metabolism)
- Carboxypeptidases
(metabolism)
- Cell Line, Tumor
- Cell Survival
(drug effects)
- Humans
- Male
- Nitric Oxide
(metabolism)
- Prolactin
(pharmacology)
- Prostatic Neoplasms
(metabolism, pathology)
- RNA, Small Interfering
(pharmacology)
- Signal Transduction
(drug effects)
- Testosterone
(pharmacology)
- Up-Regulation
(drug effects)
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