Buscail L, Saint-Laurent N, Chastre E, Vaillant J C, Gespach C, Capella G, Kalthoff H, Lluis F, Vaysse N, Susini C
INSERM U151, Institut Louis Bugnard, Toulouse, France.
Cancer Res. 1996 Apr 15;56(8):1823-7.
Five somatostatin receptor subtypes (sst1 to sst5) have been cloned. We demonstrated previously that sst2 and sst5 mediate the antiproliferative effect of the somatostatin analogues octreotide and vapreotide. Using reverse transcription-PCR, we investigated gene expression of the five receptors in 47 human normal and cancerous tissues or cell lines from pancreatic and colorectal origin. mRNAs of somatostatin receptor subtypes were detected in 98% of samples, with more than two mRNA subtypes being expressed in 55% of cases. sst1, sst4, and sst5 were heterogeneously expressed in both normal and cancerous tissues; sst3 was rarely or not expressed. sst2 was present in normal pancreatic tissues but was absent in exocrine pancreatic carcinomas and their metastases. sst2 mRNAs were detected in normal colon, sporadic polyadenomas, and 50% of Dukes' stage B and 20% of Dukes' stage C carcinomas but were undetectable in Dukes' stage D carcinomas, hepatic metastases, and adenomas from familial adenomatous polyposis. The loss of sst2 expression could represent a growth advantage in these tumors and provide an explanation for the lack of therapeutic effect of somatostatin analogues in such adenocarcinomas. A subtyping of somatostatin receptors should be carried out before considering a somatostatin analogue treatment in patients with colorectal or pancreatic cancer.
已克隆出五种生长抑素受体亚型（sst1至sst5）。我们先前已证明，sst2和sst5介导生长抑素类似物奥曲肽和伐普肽的抗增殖作用。我们采用逆转录聚合酶链反应，研究了来自胰腺和结肠直肠的47个人类正常组织、癌组织或细胞系中这五种受体的基因表达情况。98%的样本中检测到生长抑素受体亚型的信使核糖核酸，55%的病例中表达了两种以上的信使核糖核酸亚型。sst1、sst4和sst5在正常组织和癌组织中均呈异质性表达；sst3很少表达或不表达。sst2存在于正常胰腺组织中，但在外分泌性胰腺癌及其转移灶中不存在。在正常结肠、散发性息肉腺瘤、50%的杜克B期癌和20%的杜克C期癌中检测到sst2信使核糖核酸，但在杜克D期癌、肝转移灶和家族性腺瘤性息肉病的腺瘤中未检测到。sst2表达缺失可能代表这些肿瘤具有生长优势，并解释了生长抑素类似物对此类腺癌缺乏治疗效果的原因。在考虑对结直肠癌或胰腺癌患者进行生长抑素类似物治疗之前，应进行生长抑素受体亚型分型。
