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Mammalian K-ras2 is a corticosteroid-induced gene in vivo

Francine E Brennan1, Peter J Fuller

  • 1Prince Henry's Institute of Medical Research, Clayton, Victoria 3168, Australia.

Endocrinology
|March 18, 2006
PubMed

Insights

Aldosterone upregulates K-ras gene expression in the mammalian distal colon, but not the kidney. This finding suggests K-ras plays a role in corticosteroid-regulated epithelial function in the colon.

Area of Science:

  • Molecular Biology
  • Endocrinology
  • Physiology

Background:

  • Aldosterone regulates gene expression via the mineralocorticoid receptor.
  • Aldosterone-induced genes are known in the distal colon and nephron.
  • K-ras transcript was previously identified as aldosterone-induced in Xenopus A6 cells.

Purpose of the Study:

  • To determine if K-ras expression is increased in mammalian epithelia in vivo in response to aldosterone.
  • To investigate the role of K-ras in corticosteroid-regulated epithelial sodium transport in mammals.

Main Methods:

  • RNA extraction from rat kidney and distal colon after aldosterone or dexamethasone treatment.
  • Northern blot analysis and real-time RT-PCR to quantify K-ras and K-rasA isoform expression.

Main Results:

  • Aldosterone and dexamethasone induced both total K-ras and K-rasA isoform expression in the rat distal colon.
  • The time course suggests a primary transcriptional regulation.
  • Corticosteroid regulation of K-ras was not observed in the rat kidney, contrasting with amphibian studies.

Conclusions:

  • K-ras expression is regulated by corticosteroids in the mammalian distal colon.
  • This regulation appears to be transcriptional.
  • Unlike in amphibians, K-ras is not regulated by corticosteroids in the mammalian kidney, although regulation in specific cell subpopulations cannot be ruled out.

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