Characterization and significance of ACE2 and Mas receptor in human colon adenocarcinoma

J Renin Angiotensin Aldosterone Syst. 2012 Mar;13(1):202-9. doi: 10.1177/1470320311426023. Epub 2011 Nov 2.

Abstract

Introduction: A new arm of the renin-angiotensin system (RAS) has been recently characterized; this includes angiotensin converting enzyme (ACE)2 and angiotensin (Ang)1-7, a heptapeptide acting through the Mas receptor (MasR). Recent studies show that Ang1-7 has an antiproliferative action on lung adenocarcinoma cells. The aim of this study was to characterize RAS expression in human colon adenocarcinoma and to investigate whether Ang1-7 exerts an antiproliferative effect on human colon adenocarcinoma cells.

Materials and methods: Gene, protein expression and enzymatic activity of the main components of the RAS were determined on non-neoplastic colon mucosa as well as on the tumor mass and the mucosa taken 5 cm distant from it, both collected from patients with colon adenocarcinoma. Two different human colon cancer cell lines were treated with AngII and Ang1-7.

Results: The novel finding of this study was that MasR was significantly upregulated in colon adenocarcinoma compared with non-neoplastic colon mucosa, which showed little or no expression of it. ACE gene expression and enzymatic activity were also increased in the tumors. However, AngII and Ang1-7 did not have any pro-/antiproliferative effects in the cell lines studied.

Conclusions: The data suggest that upregulation of the MasR could be used as a diagnostic marker of colon adenocarcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / enzymology*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Aged
  • Angiotensin I / pharmacology
  • Angiotensin II / pharmacology
  • Angiotensin-Converting Enzyme 2
  • Caco-2 Cells
  • Cell Cycle / drug effects
  • Colonic Neoplasms / enzymology*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology
  • Female
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic / drug effects
  • HT29 Cells
  • Humans
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / enzymology
  • Intestinal Mucosa / pathology
  • Male
  • Middle Aged
  • Peptide Fragments / pharmacology
  • Peptidyl-Dipeptidase A / metabolism*
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Receptor, Angiotensin, Type 1 / metabolism
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*

Substances

  • AGTR1 protein, human
  • MAS1 protein, human
  • Peptide Fragments
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Receptor, Angiotensin, Type 1
  • Receptors, G-Protein-Coupled
  • Angiotensin II
  • Angiotensin I
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • angiotensin I (1-7)