Biagini P, Monges G, Vuaroqueaux V, Parriaux D, Cantaloube J F, De Micco P
Laboratory of Molecular Biology, Regional Center for Blood Transfusion, Marseille, France.
Life Sci. 1997;61(10):1009-18. doi: 10.1016/s0024-3205(97)00605-x.
The CCK-type B receptors are recognized by gastrin, which is known to be possibly involved in the development of gastro-intestinal cancers; alternate splicing of exon 4 of the human CCK-B receptor gene gives 2 different mRNA isoforms, the exact significance of which still remains to be elucidated. The recently described CCK-type C receptors recognize gastrin but do not discriminate between mature and immature forms of the hormone. A series of healthy and tumoral colon samples, the associated hepatic metastases and four colonic cell lines were examined for gene expression of the 2 isoforms of the CCK-B receptor and the CCK-C receptor using reverse transcription-polymerase chain reaction. Gastrin mRNA expression was also investigated. The short isoform of the CCK-B was detected in 80% of the normal colon tissues, 76.5% of the colon tumors, 100% of the metastasis samples and 75% of the colonic cell lines; whereas the long isoform, which is presumably more strongly activated by gastrin, was expressed in 50% of the normal colon samples, 23% of the colon tumors, 43% of the hepatic metastases and 1 cell line (Sk-Co15). However, although CCK-C transcript was detected in 100% of the tumors tested and gastrin mRNA in 86.5%, only 16.5% also expressed the long isoform of the CCK-B receptor. The gastrin/CCK-B receptor might therefore be involved in an hypothetic autocrine proliferative loop only in some colonic tumors, and the receptor mainly involved in this loop may well be the CCK-C receptor, since its mRNA is expressed as often as gastrin mRNA in tumors and cell lines.
胆囊收缩素B型受体可被胃泌素识别，已知胃泌素可能参与胃肠道癌症的发生发展；人胆囊收缩素B型受体基因外显子4的可变剪接产生2种不同的mRNA异构体，其确切意义仍有待阐明。最近描述的胆囊收缩素C型受体可识别胃泌素，但不能区分该激素的成熟和未成熟形式。使用逆转录-聚合酶链反应检测了一系列健康和肿瘤性结肠样本、相关的肝转移灶以及4种结肠细胞系中胆囊收缩素B型受体2种异构体和胆囊收缩素C型受体的基因表达。还研究了胃泌素mRNA的表达。胆囊收缩素B型受体的短异构体在80%的正常结肠组织、76.5%的结肠肿瘤、100%的转移样本和75%的结肠细胞系中被检测到；而可能被胃泌素更强烈激活的长异构体在50%的正常结肠样本、23%的结肠肿瘤、43%的肝转移灶和1个细胞系（Sk-Co15）中表达。然而，尽管在100%的检测肿瘤中检测到了胆囊收缩素C型受体转录本，在86.5%的肿瘤中检测到了胃泌素mRNA，但只有16.5%的肿瘤也表达了胆囊收缩素B型受体的长异构体。因此，胃泌素/胆囊收缩素B型受体可能仅在某些结肠肿瘤中参与一个假设的自分泌增殖环，而参与该环的主要受体很可能是胆囊收缩素C型受体，因为其mRNA在肿瘤和细胞系中的表达频率与胃泌素mRNA相同。
