Chopin L K, Herington A C
Centre for Molecular Biotechnology, School of Life Sciences, Queensland University of Technology, Brisbane, Queensland, Australia.
Prostate. 2001 Oct 1;49(2):116-21. doi: 10.1002/pros.1125.
Recent studies have shown that GHRH antagonists inhibit prostate tumour growth and IGF-II production both in vivo and in vitro. The mechanism underlying these observations is unknown, but may involve an interaction with a prostatic GHRH receptor (GHRH-R), raising the possibility of an autocrine pathway for the GHRH axis in the prostate.
GHRH and GHRH-R mRNA expression was examined by RT-PCR in human prostate cancer cell lines, and the authenticity of PCR products was confirmed by Southern analysis and cDNA sequencing. Immunohistochemical techniques were used to examine the expression of GHRH protein in prostate cancer cell lines.
GHRH-R (mRNA) and GHRH (mRNA and protein) are co-expressed in the ALVA-41, DU145, LNCaP and PC3 human prostate cancer cell lines.
These observations suggest the presence of an intact prostatic GHRH autocrine pathway which may stimulate prostate cell proliferation. This pathway may be disrupted by GHRH antagonists.
近期研究表明,生长激素释放激素(GHRH)拮抗剂在体内和体外均能抑制前列腺肿瘤生长及胰岛素样生长因子-II(IGF-II)的产生。这些观察结果背后的机制尚不清楚,但可能涉及与前列腺生长激素释放激素受体(GHRH-R)的相互作用,这增加了前列腺中GHRH轴存在自分泌途径的可能性。
采用逆转录聚合酶链反应(RT-PCR)检测人前列腺癌细胞系中GHRH和GHRH-R mRNA的表达,并通过Southern分析和cDNA测序确认PCR产物的真实性。运用免疫组织化学技术检测前列腺癌细胞系中GHRH蛋白的表达。
GHRH-R(mRNA)以及GHRH(mRNA和蛋白)在ALVA-41、DU145、LNCaP和PC3人前列腺癌细胞系中共同表达。
这些观察结果提示存在完整的前列腺GHRH自分泌途径,该途径可能刺激前列腺细胞增殖。此途径可能会被GHRH拮抗剂破坏。