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Aldosterone acts via the mineralocorticoid receptor to regulate gene expression. A number of aldosterone-induced genes have been characterized in the distal colon and/or the distal nephron. Using the Xenopus kidney-derived A6 cell line, the K-ras transcript of the K-ras gene was identified as aldosterone induced, with a role in epithelial sodium transport. This study sought to establish whether K-ras expression is also increased in mammalian epithelia in vivo in response to aldosterone. RNA was extracted from the kidney and distal colon of rats treated with aldosterone or dexamethasone. Northern blot analysis and real-time RT-PCR were performed using probes and primers specific for the K-rasA isoform and for total K-ras. The expression of both total K-ras and of the A isoform is induced in the distal colon by aldosterone and by dexamethasone. Given the relative abundances of the two isoforms, this would appear to indicate induction of both isoforms. The time course of the response is consistent with a primary transcriptional response. In contrast to the documented up-regulation in the amphibian kidney, we did not observe regulation by corticosteroids in the kidney. However, regulation in a subpopulation of cells cannot be excluded.

Mammalian K-ras2 Is a Corticosteroid-Induced Gene in Vivo