Expression of glutaminase is upregulated in colorectal cancer and of clinical significance

Int J Clin Exp Pathol. 2014 Feb 15;7(3):1093-100. eCollection 2014.

Abstract

Cancer cells remodel their metabolic programmes to meet the requirements of rapid proliferation. Glutaminase (GLS1) is a mitochondrial enzyme that converts glutamine to glutamate. Our aim was to investigate, for the first time, GLS1 protein expression in colorectal cancer and to evaluate its clinical significance. Immunohistochemical analysis was performed on tissue microarrays containing pairs of cancer and adjacent normal tissues from colorectal cancer patients (n=257). The expression of GLS1 protein in normal colonic tissues and colorectal cancer was measured by western blotting. Proliferation and cell death were evaluated in colorectal cancer cell lines after GLS1 inhibitor treatment. Compared with normal tissues (18.15%), we observed that the expression of GLS1 increased significantly in colorectal cancer (80.24%; P<0.0001) by immunohistochemical analysis, and the elevation of GLS1 protein expression levels in fresh colorectal cancer samples versus normal colonic tissues were also observed by western blotting. Furthermore, GLS1 expression levels were significantly associated with deeper tumour infiltration (P=0.0002), and the pathological pattern of tubular adenocarcinoma (p=0.0008). In addition, treatment with the GLS1 inhibitor suppressed proliferation and induced apoptosis in HT29 and SW480 cell lines. These results suggest that the expression of GLS1 is upregulated and correlates with clinicopathological factors in colorectal cancer. GLS1 exhibits functional importance in colon cancer tumorigenesis. Moreover, GLS1 may serve as a target for colorectal cancer therapy.

Keywords: Colorectal cancer; glutaminase; tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / enzymology*
  • Adenocarcinoma / pathology*
  • Aged
  • Blotting, Western
  • Colorectal Neoplasms / enzymology*
  • Colorectal Neoplasms / pathology*
  • Female
  • Glutaminase / biosynthesis*
  • Humans
  • Immunohistochemistry
  • Male
  • Microscopy, Fluorescence
  • Middle Aged
  • Tissue Array Analysis
  • Up-Regulation

Substances

  • Glutaminase