title: Glutaminases in slowly proliferating gastroenteropancreatic neuroendocrine neoplasms/tumors (GEP-NETs): Selective overexpression of mRNA coding for the KGA isoform.
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.
authors.affiliation: Department of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego Str., 02-106 Warsaw, Poland. Electronic address: mszeliga@imdik.pan.pl.
authors.forename: Monika
authors.initials: M
authors.lastname: Szeliga
authors.affiliation: Department of Radiology, Faculty of Medical Sciences, University of Warmia and Mazury, 30 Warszawska Str., 10-082 Olsztyn, Poland.
authors.forename: Jarosław
authors.initials: J
authors.lastname: Ćwikła
authors.affiliation: Department of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego Str., 02-106 Warsaw, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Obara-Michlewska
authors.affiliation: Department of Surgical Oncology, Maria Skłodowska-Curie Memorial Cancer Center, Institute of Oncology, 15B Wawelska Str., 02-034 Warsaw, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Cichocki
authors.affiliation: Department of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego Str., 02-106 Warsaw, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Albrecht
mesh_terms: D000328:Adult; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D005972:Glutaminase / Q000378:metabolism*; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000235:genetics* / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger; D005972:Glutaminase
keywords: Gastroenteropancreatic neuroendocrine tumors — GEP-NETs; Glutaminase isoforms; RT-PCR; mRNA