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Triple negative human breast cancers accumulate significantly less Arg‐pyrimidine moieties, than other subtype lesions (58.3)
Author(s) -
Castronovo Vincent,
Chiavarina Barbara,
Nokin MarieJulie,
Durieux Florence,
Bianchi Elettra,
Irigaray Philippe,
Uchida Koji,
Belpomme Dominique,
Bellahcène Akeila
Publication year - 2014
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.28.1_supplement.58.3
Subject(s) - methylglyoxal , breast cancer , triple negative breast cancer , pyrimidine , cancer , cancer research , adduct , enzyme , cancer cell , chemistry , biology , biochemistry , genetics , organic chemistry
Metabolic disorders influence breast cancer development and progression. Methylglyoxal (MGX), is a highly reactive glycolytic byproduct able to inflict carbonyl stress to proteins, lipids and DNA. The possible role of MGX in breast cancer development has not been yet extensively explored. We analyzed the accumulation of Arg‐pyrimidine adducts, in a series of more than 100 human breast adenocarcinoma and we observed a consistent increased of MGX adducts in cancer cells compared to the non‐tumoral counterpart. Most triple negative lesions examined exhibited low accumulation of Arg‐pyrimidine residues compared other subtypes. Intriguingly, the level of expression of glyoxalase 1 (Glo‐1), an enzyme that detoxifies MGX, was similar in both triple negative and other subtype lesions, suggesting a potential difference in the Glo‐1 activity. This hypothesis is supported by our preliminary results on breast cancer cell lines, showing that triple negative cells are more efficient to respond to treatment with MGX by increasing the activity of Glo‐1. Our study represent the first observation that Arg‐pyrimidine adducts accumulation is a consistent event in human breast cancer with a differential detection between triple negative and other breast cancer subtypes. Our preliminary data suggest that methylglyoxal production and detoxification could be a molecular link between metabolic diseases and breast cancer. Grant Funding Source : This study is supported by Founds for National Research (FNRS), Belgium