Morgan, K., Stavrou, E., Leighton, S. P. , Miller, N., Sellar, R. and Millar, R. P. (2011) Elevated GnRH receptor expression plus GnRH agonist treatment inhibits the growth of a subset of papillomavirus 18-immortalized human prostate cells. Prostate, 71(9), pp. 915-928. (doi: 10.1002/pros.21308) (PMID:21541969)
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Abstract
Background and Aims: Human metastatic prostate cancer cell growth can be inhibited by GnRH analogs but effects on virus‐immortalized prostate cells have not been investigated. Methods: Virus‐immortalized prostate cells were stably transfected with rat GnRH receptor cDNA and levels of GnRH binding were correlated with GnRH effects on signaling, cell cycle, growth, exosome production, and apoptosis. Results: High levels of cell surface GnRH receptor occurred in transfected papillomavirus‐immortalized WPE‐1‐NB26 epithelial cells but not in non‐tumourigenic RWPE‐1, myoepithelial WPMY‐1 cells, or SV40‐immortalized PNT1A. Endogenous cell surface GnRH receptor was undetectable in non‐transfected cells or cancer cell lines LNCaP, PC3, and DU145. GnRH receptor levels correlated with induction of inositol phosphates, elevation of intracellular Ca2+, cytoskeletal actin reorganization, modulation of ERK activation and cell growth‐inhibition with GnRH agonists. Hoechst 33342 DNA staining‐cell sorting indicated accumulation of cells in G2 following agonist treatment. Release of exosomes from transfected WPE‐1‐NB26 was unaffected by agonists, unlike induction observed in HEK293[SCL60] cells. Increased PARP cleavage and apoptotic body production were undetectable during growth‐inhibition in WPE‐1‐NB26 cells, contrasting with HEK293[SCL60]. EGF receptor activation inhibited GnRH‐induced ERK activation in WPE‐1‐NB26 but growth‐inhibition was not rescued by EGF or PKC inhibitor Ro320432. Growth of cells expressing low levels of GnRH receptor was not affected by agonists. Conclusions: Engineered high‐level GnRH receptor activation inhibits growth of a subset of papillomavirus‐immortalized prostate cells. Elucidating mechanisms leading to clone‐specific differences in cell surface GnRH receptor levels is a valuable next step in developing strategies to exploit prostate cell anti‐proliferation using GnRH agonists.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Leighton, Dr Samuel |
| Authors: | Morgan, K., Stavrou, E., Leighton, S. P., Miller, N., Sellar, R., and Millar, R. P. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > General Practice and Primary Care |
| Journal Name: | Prostate |
| Publisher: | Wiley |
| ISSN: | 0270-4137 |
| ISSN (Online): | 1097-0045 |
| Published Online: | 06 December 2010 |
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