Kubota A, Yamada Y, Kagimoto S, Shimatsu A, Imamura M, Tsuda K, Imura H, Seino S, Seino Y
Department of Metabolism and Clinical Nutrition, Kyoto University Faculty of Medicine, Japan.
J Clin Invest. 1994 Mar;93(3):1321-5. doi: 10.1172/JCI117090.
The presence of somatostatin receptors has been demonstrated in various endocrine tumors as well as in normal tissues. We recently have cloned five human somatostatin receptor subtypes (SSTR1-SSTR5). These mRNAs are expressed in a tissue-specific manner. In this study, we have determined the somatostatin receptor subtypes expressed in various endocrine tumors using a reverse transcriptase polymerase chain reaction method. In two cases of glucagonoma and its metastatic lymph nodes in one case, all the SSTR subtype mRNAs except SSTR5 mRNA were expressed. In four cases of insulinoma, SSTR1 and SSTR4 mRNAs were detected, but SSTR2 mRNA was not detected in one case and SSTR3 mRNA was not detected in two cases, indicating a heterogeneous expression of SSTR subtypes in insulinomas. Interestingly, SSTR3 mRNA, which is highly expressed in rat pancreatic islets, is not expressed in normal human pancreatic islets, while SSTR1, SSTR2, and SSTR4 mRNAs are expressed. In three cases of pheochromocytoma, SSTR1 and SSTR2 mRNAs were detected, showing an expression pattern identical to that of normal adrenal gland. In a carcinoid, SSTR1 and SSTR4 mRNAs were detected. We have also found that human SSTR2 shows a high affinity for SMS 201-995, which has been used clinically for the treatment of endocrine tumors. Since SMS 201-995 was effective in the treatment of a patient with glucagonoma in which SSTR2 mRNA was present, but had no effect in a patient with carcinoid in which SSTR2 mRNA was not detected, this study suggests that the efficacy of SMS 201-995 may depend, at least in part, on the expression of SSTR2 in tumors.
生长抑素受体已在多种内分泌肿瘤以及正常组织中得到证实。我们最近克隆了5种人类生长抑素受体亚型（SSTR1 - SSTR5）。这些信使核糖核酸（mRNA）以组织特异性方式表达。在本研究中，我们使用逆转录聚合酶链反应方法确定了多种内分泌肿瘤中表达的生长抑素受体亚型。在两例胰高血糖素瘤及其一例转移性淋巴结中，除SSTR5 mRNA外，所有SSTR亚型mRNA均有表达。在四例胰岛素瘤中，检测到SSTR1和SSTR4 mRNA，但有一例未检测到SSTR2 mRNA，两例未检测到SSTR3 mRNA，表明胰岛素瘤中SSTR亚型表达具有异质性。有趣的是，在大鼠胰岛中高表达的SSTR3 mRNA在正常人类胰岛中不表达，而SSTR1、SSTR2和SSTR4 mRNA则有表达。在三例嗜铬细胞瘤中，检测到SSTR1和SSTR2 mRNA，其表达模式与正常肾上腺相同。在一例类癌中，检测到SSTR1和SSTR4 mRNA。我们还发现人类SSTR2对SMS 201 - 995具有高亲和力，SMS 201 - 995已临床用于治疗内分泌肿瘤。由于SMS 201 - 995对存在SSTR2 mRNA的胰高血糖素瘤患者有效，但对未检测到SSTR2 mRNA的类癌患者无效，本研究表明SMS 201 - 995的疗效可能至少部分取决于肿瘤中SSTR2的表达。
