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Analysis of ethanol metabolic enzymes in primary human mammary epithelial cells and MCF‐10A cells: possible participation of CYP2E1 in ethanol‐induced oxidative stress and epidermal growth factor receptor (EGFR) activation
Author(s) -
Rodríguez-Fragoso Lourdes,
Buitimea Angel Leon,
Lauer Fredine,
Thompson Todd,
Bowels Harmony,
Burchiel Scott
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.758.4
Subject(s) - oxidative stress , chemistry , mcf 7 , cyp2e1 , oxidative phosphorylation , epidermal growth factor receptor , cancer research , cell culture , microbiology and biotechnology , enzyme , cancer cell , receptor , biochemistry , medicine , biology , cancer , human breast , cytochrome p450 , genetics
Ethanol (EtOH) consumption is a well‐established risk factor for breast cancer in women. However, the mechanism by which EtOH exerts its carcinogenic activity in breast tissue remains known. In the present work, we analyze the ethanol metabolic enzymes in primary human mammary epithelial cells (HMEC) and MCF10A cells and to study the role of those enzymes in ethanol‐ induced oxidative stress and EGFR activation. Our results show that EtOH decreased CYP2E1 protein expression at 10, 30 and 100 mM when cells were treated every 12 h for 3 days. We also found that 30 and 100 mM EtOH increased ROS levels after 2 h treatment in CYP2E1over‐expressing 4.1.2E1 cells. Additionally, we found that in CYP2E1over‐expressing 4.1.2E1 cells increased the level of pY1086 EGFR phosphorylation after 18 h ethanol treatment. These studies suggest that ethanol can transactivate EGFR and activate downstream cell signaling in MCF10A cells, mediated by oxidative stress. These studies were supported in part by NIH RO1 ES‐07259 and by CONACYT ‐Mexico a Fellowship to Angel León‐Buitimea number 212849.