title: Triple negative tumors accumulate significantly less methylglyoxal specific adducts than other human breast cancer subtypes.
abstract: Metabolic syndrome and type 2 diabetes are associated with increased risk of breast cancer development and progression. Methylglyoxal (MG), a glycolysis by-product, is generated through a non-enzymatic reaction from triose-phosphate intermediates. This dicarbonyl compound is highly reactive and contributes to the accumulation of advanced glycation end products. In this study, we analyzed the accumulation of Arg-pyrimidine, a MG-arginine adduct, in human breast adenocarcinoma and we observed a consistent increase of Arg-pyrimidine in cancer cells when compared with the non-tumoral counterpart. Further immunohistochemical comparative analysis of breast cancer subtypes revealed that triple negative lesions exhibited low accumulation of Arg-pyrimidine compared with other subtypes. Interestingly, the activity of glyoxalase 1 (Glo-1), an enzyme that detoxifies MG, was significantly higher in triple negative than in other subtype lesions, suggesting that these aggressive tumors are able to develop an efficient response against dicarbonyl stress. Using breast cancer cell lines, we substantiated these clinical observations by showing that, in contrast to triple positive, triple negative cells induced Glo-1 expression and activity in response to MG treatment. This is the first report that Arg-pyrimidine adduct accumulation is a consistent event in human breast cancer with a differential detection between triple negative and other breast cancer subtypes.
authors: Metastasis Research Laboratory, GIGA-Cancer, University of Liège, Liège, Belgium.
authors: Barbara
authors: B
authors: Chiavarina
authors: Metastasis Research Laboratory, GIGA-Cancer, University of Liège, Liège, Belgium.
authors: Marie-Julie
authors: MJ
authors: Nokin
authors: Metastasis Research Laboratory, GIGA-Cancer, University of Liège, Liège, Belgium.
authors: Florence
authors: F
authors: Durieux
authors: Department of Anatomy and Pathology, University of Liège, Liège, Belgium.
authors: Elettra
authors: E
authors: Bianchi
authors: Metastasis Research Laboratory, GIGA-Cancer, University of Liège, Liège, Belgium.
authors: Andrei
authors: A
authors: Turtoi
authors: Metastasis Research Laboratory, GIGA-Cancer, University of Liège, Liège, Belgium.
authors: Olivier
authors: O
authors: Peulen
authors: Metastasis Research Laboratory, GIGA-Cancer, University of Liège, Liège, Belgium.
authors: Paul
authors: P
authors: Peixoto
authors: Association for Research and Treatments Against Cancer (ARTAC), Paris, France.
authors: Philippe
authors: P
authors: Irigaray
authors: Laboratory of Food and Biodynamics, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors: Koji
authors: K
authors: Uchida
authors: Association for Research and Treatments Against Cancer (ARTAC), Paris, France.
authors: Dominique
authors: D
authors: Belpomme
authors: Department of Anatomy and Pathology, University of Liège, Liège, Belgium.
authors: Philippe
authors: P
authors: Delvenne
authors: Metastasis Research Laboratory, GIGA-Cancer, University of Liège, Liège, Belgium.
authors: Vincent
authors: V
authors: Castronovo
authors: Metastasis Research Laboratory, GIGA-Cancer, University of Liège, Liège, Belgium.
authors: Akeila
authors: A
authors: Bellahcène
mesh_terms: D001120:Arginine / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007791:Lactoylglutathione Lyase / Q000378:metabolism*; D061986:MCF-7 Cells; D011743:Pyrimidines / Q000378:metabolism*; D011765:Pyruvaldehyde / Q000378:metabolism*; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D017127:Glycation End Products, Advanced; D011743:Pyrimidines; D011765:Pyruvaldehyde; D001120:Arginine; D007791:Lactoylglutathione Lyase