Novel expression of the angiotensinogen gene in a rat pancreatic islet cell line. Transcriptional regulation by glucocorticoids

Angiotensinogen gene expression has a broad tissue specificity. Whereas angiotensinogen mRNA is undetectable in normal rat pancreas, we have identified angiotensinogen mRNA in all tumors and cell lines derived from a rat islet cell line, RIN-r. A subclone with the highest angiotensinogen mRNA levels, 1056A, secreted N-glycosylated angiotensinogen. Angiotensinogen mRNA of 1056A cells was ~ 200 nucleotides longer than that of liver, and this was shown to be due to an extension of the 3'-untranslated region. Dexamethasone increased angiotensinogen mRNA levels ~ 9-fold above control, and this increase was linear over 110 h, indicating a half-life of greater than 55 h for angiotensinogen mRNA during hexamethasone induction. This effect of dexamethasone was inhibited by the glucocorticoid antagonist RU 38486. Dexamethasone increased angiotensinogen gene transcription ~ 5-fold in a nuclear run-on assay. These results demonstrate that dexamethasone induction of angiotensinogen mRNA levels in 1056A cells is due, at least in part, to a transcriptional response and that 1056A cells will be useful for the study of angiotensinogen gene regulation and the identification of glucocorticoid regulatory sequences.