Glutaminases in slowly proliferating gastroenteropancreatic neuroendocrine neoplasms/tumors (GEP-NETs): Selective overexpression of mRNA coding for the KGA isoform

Exp Mol Pathol. 2016 Feb;100(1):74-8. doi: 10.1016/j.yexmp.2015.11.017. Epub 2015 Nov 12.

Abstract

Glutamine (Gln) is a crucial metabolite in cancer cells of different origin, and the expression and activity of different isoforms of the Gln-degrading enzyme, glutaminase (GA), have variable implications for tumor growth and metabolism. Human glutaminases are encoded by two genes: the GLS gene encodes the kidney-type glutaminases, KGA and GAC, while the GLS2 gene encodes the liver-type glutaminases, GAB and LGA. Recent studies suggest that the GAC isoform and thus high GAC/KGA ratio, are characteristic of highly proliferating tumors, while GLS2 proteins have an inhibitory effect on tumor growth. Here we analyzed the expression levels of distinct GA transcripts in 7 gastroenteropancreatic neuroendocrine tumors (GEP-NETs) with low proliferation index and 7 non-neoplastic tissues. GEP-NETs overexpressed KGA, while GAC, which was the most abundant isoform, was not different from control. The expression of the GLS2 gene showed tendency towards elevation in GEP-NETs compared to control. Collectively, the expression pattern of GA isoforms conforms to the low proliferative capacity of GEP-NETs encompassed in this study.

Keywords: Gastroenteropancreatic neuroendocrine tumors — GEP-NETs; Glutaminase isoforms; RT-PCR; mRNA.

MeSH terms

  • Adult
  • Cell Proliferation*
  • Cell Survival / genetics
  • Cell Survival / physiology
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Glutaminase / metabolism*
  • Humans
  • Intestinal Neoplasms / genetics*
  • Intestinal Neoplasms / metabolism*
  • Middle Aged
  • Neuroendocrine Tumors / genetics*
  • Neuroendocrine Tumors / metabolism*
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism*
  • Protein Isoforms
  • RNA, Messenger / genetics*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism*

Substances

  • Protein Isoforms
  • RNA, Messenger
  • Glutaminase

Supplementary concepts

  • Gastro-enteropancreatic neuroendocrine tumor