Underexpression of mineralocorticoid receptor in colorectal carcinomas and association with VEGFR-2 overexpression

J Gastrointest Surg. 2007 Nov;11(11):1521-8. doi: 10.1007/s11605-007-0234-8. Epub 2007 Aug 17.

Abstract

Background: The human mineralocorticoid receptor (MR) is a steroid receptor widely expressed in colorectal mucosa. A significant role for the MR in the reduction of vascular endothelial growth factor receptor-2 (VEGFR-2) mRNA levels has been demonstrated in vitro. To evaluate a potential contribution of MR to colorectal carcinoma progression, we analyzed the expression of MR in relation to VEGFR-2.

Methods: Fresh human colorectal cancer tissue and adjacent normal mucosa were harvested from 48 consecutive patients. MR and VEGFR-2 mRNA expression levels were determined by real-time reverse transcriptase-polymerase chain reaction and correlated with clinicopathological parameters.

Results: A decline of MR expression was observed in all carcinomas compared to normal mucosa. Expression of MR was a median of 11-fold lower in carcinoma compared to the normal mucosa, irrespective of the location, size, stage, and differentiation. MR was a median of 20-fold underexpressed in carcinomas with VEGFR-2 overexpression vs only 9-fold in carcinomas with VEGFR-2 underexpression (p = 0.035, Mann-Whitney test).

Conclusions: These findings support the hypothesis that reduction of MR expression may be one of the early events involved in colorectal carcinoma progression. The inverse association between MR and VEGFR-2 expression in carcinoma suggests a potential tumor-suppressive function for MR.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Differentiation
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Disease Progression
  • Female
  • Humans
  • Intestinal Mucosa / metabolism
  • Male
  • Middle Aged
  • RNA, Messenger / analysis
  • Receptors, Mineralocorticoid / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism*

Substances

  • RNA, Messenger
  • Receptors, Mineralocorticoid
  • Vascular Endothelial Growth Factor Receptor-2