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Departments of Medicine [C. W., R. C., D. J. D.], Clinical Biochemistry [D. J. D.], Genetics [D. J. D.], and Physiology [K. M. S., P. L. B.], University of Toronto, Toronto, Ontario, Canada
Glucocorticoid regulation of peptide hormone gene expression was studied in two cell lines derived from rodent islet cell tumors. In rat RIN1056A cells, dexamethasone reduced the levels of glucagon mRNA transcripts while markedly inducing the expression of the angiotensinogen gene. In contrast, dexamethasone had no effect on the regulation of glucagon gene expression in hamster InR1-G9 cells. Wild type InR1-G9 cells did not support the induction of the murine mammary tumor virus promoter by glucocorticoids, suggesting that these cells lacked the necessary cellular factor(s) for glucocorticoid responsiveness. Introduction of the glucocorticoid receptor into wild type InR1-G9 cells restored glucocorticoid induction of the murine mammary tumor virus promoter, but not glucocorticoid regulation of glucagon gene expression. Dexamethasone treatment of Sprague-Dawley rats had no effect on the levels of pancreatic glucagon mRNA transcripts. The results of these studies demonstrate that glucocorticoid regulation of glucagon gene expression is restricted to the immortalized RIN1056A cell line, providing additional evidence for cell-specific diversity in the regulation of peptide hormone gene expression in neuroendocrine tumors.
1 This work was supported in part by grants from the Medical Research Council of Canada and the National Cancer Institute. D. J. D. is a Career Scientist of the Ontario Ministry of Health, and P. L. B. is a Research Scholar of the Canadian Diabetes Association. C. W. and K. M. S. are fellows of the Canadian Diabetes Association, and R. C. is an ICI Pharma-MRC fellow.
2 To whom requests for reprints should be addressed, at Toronto General Hospital, 200 Elizabeth Street CCRW3-838, Toronto, Ontario, Canada M5G 2C4.
Received 10/12/90. Accepted 12/ 5/90.
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