Nelson J B, Chan-Tack K, Hedican S P, Magnuson S R, Opgenorth T J, Bova G S, Simons J W
James Buchanan Brady Urological Institute Research Laboratories, Johns Hopkins Hospital, Baltimore, Maryland 21287-2411, USA.
Cancer Res. 1996 Feb 15;56(4):663-8.
The potent vasoconstrictor endothelin-1 (ET-1) is at its highest concentration in the normal human ejaculate and is associated with the progression of metastatic prostate cancer. ET-1 protein expression is detected in situ in 14 of 14 primary cancers and 14 of 16 metastatic sites of human prostatic carcinoma. Exogenous ET-1 induces prostate cancer proliferation directly and enhances the mitogenic effects of insulin-like growth factor I, insulin-like growth factor II, platelet-derived growth factor, basic fibroblast growth factor, and epidermal growth factor in serum-free conditions in vitro. The ETA-selective receptor antagonist A-127722 inhibits ET-1-stimulated growth, but the ETB-selective receptor antagonist BQ-788 does not. ET-3, an ETB-selective agonist, also had no effect on prostate cancer growth. No specific ETB-binding sites could be demonstrated in any established human prostate cancer cell line tested, and ETB mRNA, detected by reverse transcription PCR, was reduced. The predominance of ETB binding on human benign prostatic epithelial tissue is not present in metastatic prostate cancer by autoradiography. In human prostate cancer progression to metastases, ET-1 and ETA expression are retained, whereas ETB receptor expression is reduced.
强效血管收缩剂内皮素-1（ET-1）在正常人类射精液中的浓度最高，且与转移性前列腺癌的进展相关。在14例原发性前列腺癌及16个转移性前列腺癌病灶中的14个中，可原位检测到ET-1蛋白表达。外源性ET-1可直接诱导前列腺癌增殖，并在无血清体外培养条件下增强胰岛素样生长因子I、胰岛素样生长因子II、血小板衍生生长因子、碱性成纤维细胞生长因子及表皮生长因子的促有丝分裂作用。ETA选择性受体拮抗剂A-127722可抑制ET-1刺激的生长，但ETB选择性受体拮抗剂BQ-788则无此作用。ETB选择性激动剂ET-3对前列腺癌生长也无影响。在所检测的任何已建立的人类前列腺癌细胞系中均未证实有特异性ETB结合位点，且通过逆转录聚合酶链反应检测到的ETB mRNA减少。通过放射自显影术发现，转移性前列腺癌中不存在ETB结合在人类良性前列腺上皮组织上的优势现象。在人类前列腺癌进展为转移癌的过程中，ET-1和ETA表达得以保留，而ETB受体表达则减少。
