Corjay M H, Dobrzanski D J, Way J M, Viallet J, Shapira H, Worland P, Sausville E A, Battey J F
Laboratory of Neurochemistry, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
J Biol Chem. 1991 Oct 5;266(28):18771-9.
Bombesin-like peptides have been implicated as autocrine growth factors influencing the pathogenesis and progression of some human lung carcinoma cells. To determine the pharmacologic and structural properties of the bombesin receptors expressed in human lung carcinoma cells, cDNA clones encoding a human gastrin-releasing peptide receptor (GRP-R) and a pharmacologically distinct neuromedin-B preferring bombesin-receptor (NMB-R) were isolated from a human small cell lung carcinoma cell line (NCI-H345). After expression in Xenopus oocytes, a GRP-R-specific antagonist was effective in blocking responses elicited from the cloned GRP-R, but not the NMB-R. Both GRP-R and NMB-R mRNA expression was detected at varying levels in a panel of human lung cancer cell lines. These results indicate heterogeneity of bombesin receptor subtypes exists in human lung carcinoma cells and should be considered in the design of bombesin receptor antagonists intended to inhibit tumor cell growth.
蛙皮素样肽被认为是影响某些人类肺癌细胞发病机制和进展的自分泌生长因子。为了确定人类肺癌细胞中表达的蛙皮素受体的药理学和结构特性，从人类小细胞肺癌细胞系（NCI-H345）中分离出编码人类胃泌素释放肽受体（GRP-R）和药理学上不同的偏爱神经降压素B的蛙皮素受体（NMB-R）的cDNA克隆。在非洲爪蟾卵母细胞中表达后，一种GRP-R特异性拮抗剂可有效阻断克隆的GRP-R引发的反应，但不能阻断NMB-R的反应。在一组人类肺癌细胞系中检测到不同水平的GRP-R和NMB-R mRNA表达。这些结果表明人类肺癌细胞中存在蛙皮素受体亚型的异质性，在设计旨在抑制肿瘤细胞生长的蛙皮素受体拮抗剂时应予以考虑。
