Premium
Glutamine Synthetase plays a dual role in the dependence of human cancer cells from glutamine
Author(s) -
Chiu Martina,
Tardito Saverio,
Gazzola Renata Franchi,
Bianchi Massimiliano G.,
Uggeri Jacopo,
Bussolati Ovidio
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.145.18
Subject(s) - glutamine synthetase , glutamine , extracellular , cell culture , cancer cell , intracellular , cancer research , biology , microbiology and biotechnology , medicine , chemistry , biochemistry , cancer , amino acid , genetics
GS‐positive and GS‐negative human cancer cells were compared to study the relationships between Glutamine Synthetase (GS) and the sensitivity to Gln depletion. Gln depletion was obtained with either Gln withdrawal or L‐asparaginase treatment. β‐Catenin‐mutated human Hepatocellular Carcinoma (HCC) HepG2 cells highly expressed GS mRNA under control conditions (4 mM extracellular Gln) and exhibited increased GS protein and activity upon Gln depletion. Compared with β‐catenin wild type Huh‐7 cells, HepG2 cells had higher intracellular levels of Gln under control conditions but were more sensitive to Gln starvation, thus exhibiting features of Gln addiction. Two oligodendroglioma cell lines, Hs683 and HOG, failed to express GS protein even upon prolonged asparaginase treatment but were much more sensitive to Gln starvation than GS‐positive U87 glioblastoma cells. Upon Gln starvation, GS inhibitors synergized cytotoxicity in GS‐positive HCC and glioblastoma cells, but were without effect in GS negative oligodendroglioma cells. Thus, under conditions of Gln shortage the adaptive increase of GS protein is a pro‐survival factor, while GS overexpression in Gln‐fed cells may be a marker of Gln addiction.