Sun B, Halmos G, Schally A V, Wang X, Martinez M
Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, Louisiana 70112, USA.
Prostate. 2000 Mar 1;42(4):295-303. doi: 10.1002/(sici)1097-0045(20000301)42:4<295::aid-pros7>3.0.co;2-b.
Bombesin-like peptides can function as autocrine or paracrine growth factors and stimulate the growth of some cancer cells, including human prostate cancer. Three bombesin receptor subtypes, termed gastrin-releasing peptide receptor (GRPR), neuromedin B receptor (NMBR), and bombesin receptor subtype 3 (BRS-3), have been identified in rodents and humans.
We investigated the presence and characteristics of the functional receptors for bombesin/GRP in human prostate adenocarcinoma specimens by radio-receptor assay and the mRNA expression of the three bombesin receptor subtypes by RT-PCR.
Of the 80 specimens of primary prostate cancer examined by receptor binding assays, 50 ( approximately 63%) showed high-affinity, low-capacity binding sites for bombesin/GRP, and 12 of these 50 receptor-positive specimens also showed a second binding site. Of the 22 prostate cancer specimens analyzed by RT-PCR, 20 (91%) expressed GRPR mRNA, 3 (14%) showed NMBR mRNA, and 2 ( approximately 9%) revealed BRS-3 mRNA. No correlation was observed between receptor expression and patients' age or pathological data.
The detection of a wide distribution of bombesin/GRP receptors in human prostate carcinomas supports the view that they may be involved in modulation of tumor progression and suggests that approaches based on binding of bombesin receptor antagonists or new targeted cytotoxic bombesin analogs to prostate cancers could be considered for the therapy.
蛙皮素样肽可作为自分泌或旁分泌生长因子,刺激包括人前列腺癌在内的某些癌细胞生长。在啮齿动物和人类中已鉴定出三种蛙皮素受体亚型,即胃泌素释放肽受体(GRPR)、神经降压素B受体(NMBR)和蛙皮素受体亚型3(BRS-3)。
我们通过放射受体分析研究了人前列腺腺癌标本中蛙皮素/GRP功能受体的存在和特征,并通过RT-PCR研究了三种蛙皮素受体亚型的mRNA表达。
在通过受体结合分析检测的80例原发性前列腺癌标本中,50例(约63%)显示出对蛙皮素/GRP的高亲和力、低容量结合位点,这50例受体阳性标本中有12例还显示出第二个结合位点。在通过RT-PCR分析的22例前列腺癌标本中,20例(91%)表达GRPR mRNA,3例(14%)显示NMBR mRNA,2例(约9%)显示BRS-3 mRNA。未观察到受体表达与患者年龄或病理数据之间的相关性。
在人前列腺癌中检测到广泛分布的蛙皮素/GRP受体,支持了它们可能参与肿瘤进展调节的观点,并表明基于蛙皮素受体拮抗剂或新型靶向细胞毒性蛙皮素类似物与前列腺癌结合的方法可考虑用于治疗。