Oncotarget

Research Papers:

Triple negative tumors accumulate significantly less methylglyoxal specific adducts than other human breast cancer subtypes

Barbara Chiavarina, Marie-Julie Nokin, Florence x Florence Durieux, Elettra Bianchi, Andrei x Andrei Turtoi, Olivier Peulen, Paul Peixoto, Philippe Irigaray, Koji Uchida, Dominique Belpomme, Philippe Delvenne, Vincent Castronovo and Akeila Bellahcène _

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Oncotarget. 2014; 5:5472-5482. https://doi.org/10.18632/oncotarget.2121

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Abstract

Barbara Chiavarina1,*, Marie-Julie Nokin1,*, Florence Durieux1, Elettra Bianchi2, Andrei Turtoi1, Olivier Peulen1, Paul Peixoto1, Philippe Irigaray3, Koji Uchida4, Dominique Belpomme3, Philippe Delvenne2, Vincent Castronovo1 and Akeila Bellahcène1

1 Metastasis Research Laboratory, GIGA-Cancer, University of Liège, Liège, Belgium

2 Department of Anatomy and Pathology, University of Liège, Liège, Belgium

3 Association for Research and Treatments Against Cancer (ARTAC), Paris, France

4 Laboratory of Food and Biodynamics, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan

* These Authors contributed equally to this work

Correspondence:

Akeila Bellahcène, email:

Keywords: methylglyoxal, breast cancer, advanced glycation end-products, Arg-pyrimidine adducts, glyoxalase 1

Received: April 11, 2014 Accepted: June 18, 2014 Published: June 20, 2014

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.


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