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Expression of the Calcium-Sensing Receptor in Gastrinomas

Digestive Diseases Branch (S.U.G., P.L.P., F.G., R.T.J., J.S.) and Metabolic Diseases Branch (P.K.G., A.M.S.), National Institute of Diabetes and Digestive and Kidney Diseases, and Hematopathology Section, Laboratory of Pathology, National Cancer Institute (M.R.), National Institutes of Health, Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Dr. Robert T. Jensen, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, Building 10, Room 9C-103, 10 Center Drive, MSC 1804, Bethesda, Maryland 20892-1804.

Extracellular calcium levels are able to influence the secretion of gastrin by gastrinomas and possibly affect the growth pattern. The molecular mechanisms of these functions are not known. The purpose of the present study was to investigate the presence of the calcium-sensing receptor (CaR) in 10 gastrinomas and determine the extent of expression in the tumors. The amounts of CaR messenger ribonucleic acid in eight tumors were determined by quantitative RT-PCR. Protein expression was analyzed by Western blot and immunohistochemistry using a monoclonal antibody (ADD). CaR messenger ribonucleic acid was detected in all gastrinomas with levels ranging from 0.04–3.16 times the amount of ß-actin transcripts. The Western blot showed a major immunoreactive band at 250 kDa and a minor at 140 kDa, corresponding to the receptor dimer and monomer, respectively. Immunohistochemistry demonstrated variable membranous staining in all gastrinomas and normal pancreatic islets. No staining was observed in the normal liver, lymph node, or exocrine pancreas. We conclude that the CaR is present in all gastrinomas, with expression varying by 80-fold. It probably contributes to the calcium-stimulated gastrin release by gastrinomas. Whether the density of the CaR is a determining factor of the magnitude of this gastrin release or plays a role in regulating the growth pattern of the gastrinoma, as it does in other cells, remains unclear at present.

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