Expression of gonadotropin-releasing hormone (GnRH) and GnRH receptor mRNA in prostate cancer cells and effect of GnRH on the proliferation of prostate cancer cells

Abstract

The purpose of this study was to determine the production of gonadotropin-releasing hormone (GnRH), the co-occurrence of GnRH receptors in prostate cancer cells, and the effect of GnRH on prostate cancer cell proliferation. Four human prostate cancer cell lines were studied. LNCaP is an androgen sensitive prostate cancer cell line, DU-145 and PC-3 are androgen resistant, and TSU-Pr1 is uncharacterized. The expression of GnRH and GnRH receptor mRNAs were assessed by in situ hybridization and the effect of exogenous GnRH on proliferation of prostate cancer cells was measured by thymidine incorporation assay. GnRH mRNA expression, determined by in situ hybridization, was found in 83.48% of the LNCaP, 89.7% of the TSU-Pr1, 86.2% of the PC-3 and 95.3% of the DU-145. Signals of GnRH receptor mRNA were detected in more than 95% of the cells of all four cell lines. The proliferation of the prostate cancer cells grown in media supplemented with peptide hormone lacking charcoal-stripped serum was significantly (P < 0.05) suppressed. No significant effect of GnRH on the proliferation of all four prostate cancer cells was observed. In summary, prostate cancer cells produced GnRH and its receptors, and exogenous GnRH treatment did not affect the prostate cancer cell proliferation. The existence of GnRH and GnRH receptor mRNA in the same cell suggests that the role of GnRH produced by prostate cancer cells would be autocrine.

Signalling and anti-proliferative effects mediated by gonadotrophin-releasing hormone receptors after expression in prostate cancer cells using recombinant adenovirus

“…This is in apparent contradiction of earlier work showing direct inhibition of PC3 cell proliferation by GnRH analogues (Limonta et al 1992, Palyi et al 1999 but is in accord with the lack of endogenous receptor binding and signalling (data herein) and with previous work showing no inhibition of proliferation (Bahk et al 1998). The reasons for such discrepancies are unknown but could relate to culture conditions, particularly since these have been shown to cause selection of functionally distinct sub-populations of PC3 cells (Festuccia et al 2000).…”

“…However, GnRH receptors (GnRH-Rs) (often along with GnRH) may also be expressed in these cancers (Miller et al 1985, Emons & Schally 1994, Emons et al 1996, Schally 1999, Schally et al 2001. Interest in these receptors stems primarily from the fact that GnRH analogues (or cytotoxic derivatives thereof ) can inhibit proliferation of cell lines derived from such cancers, implying that such direct effects may contribute to the efficacy of GnRH analogues in cancer therapy (Miller et al 1985, Qayum et al 1990, Limonta et al 1992, Dondi et al 1994, Emons & Schally 1994, Emons et al 1997, Bahk et al 1998, Palyi et al 1999, Schally 1999, Halmos et al 2000, Ravenna et al 2000, Schally et al 2001.…”

Luteinizing hormone-releasing hormone receptor–targeted deslorelin-docetaxel conjugate enhances efficacy of docetaxel in prostate cancer therapy

“…This is a very important consideration in the design and synthesis of targeted anticancer agents. To confirm the activity of the conjugate, we further tested its efficacy in LNCaP, a hormonedependent cell line, and PC-3, a hormone-independent cell line, two cell lines overexpressing the LHRH-R (38). Our antiproliferative studies showed that the deslorelin-docetaxel conjugate is significantly more cytotoxic in both cell lines compared with docetaxel alone.…”

Gonadotropin-Releasing Hormone Induces Apoptosis of Prostate Cancer Cells

“…However, there is increasing evidence showing that the effects of GnRH-a on carcinoma of the prostate are mediated not only through suppression of gonadal steroids, but also through a direct effect on cell growth (33)(34)(35)(36). This effect may indicate that besides its effect on androgen-sensitive carcinoma of the prostate, GnRH-a may be efficient also in the treatment of hormonerefractory prostate cancer.…”