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Loss of sst2 Somatostatin Receptor Gene Expression in Human Pancreatic and Colorectal Cancer¹

INSERM U151, Institut Louis Bugnard, I avenue J. Poulhès, CHU Rangueil, 31054 Toulouse, Cédex, France [L. B., N. S-L., N. V., C. S.]; INSERM U55 and Service de Chirurgie Digestive, Hôpital Saint Antoine, 75012 Paris, France [E. C., J-C. V., C. G.]; Laboratori d'Investigacio Gastrointestinal, Institut de Recerca, Hospital de la Santa Creu I Sant Pau, 08025 Barcelona, Spain [G. C., F. L.]; and Research Unit Molecular Oncology, University Hospital, 24105 Kiel, Germany [H. K.]

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.

¹ Supported in part by Grant 6755 from the Association pour la Recherche contre le Cancer; Grant 9200045 from the Conseil Régional Midi Pyrénées; a grant from the Institut de Recherche des Maladies de l'Appareil Digestif; Grant SAL91-0873 from the Plan Nacional I + D, Spain; and Grant FIS 94-0001-1 from The Fondo de Investigaciones Sanitarias, Spain.

² To whom requests for reprints should be addressed. Phone: (33) 61 32 24 01; Fax: (33) 62 26 40 12.

Received 10/20/95. Accepted 2/14/96.

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