Ethanol-induced oxidative stress is associated with EGF receptor phosphorylation in MCF-10A cells overexpressing CYP2E1.
Breast cancer is the most common cancer and the second leading cause of cancer-related mortality worldwide. The etiology of breast cancer is very diverse and 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 unknown. CYP2E1 is known to metabolize ethanol and produce reactive oxygen species (ROS), including superoxide in epithelial cells. Therefore, in the present studies, we investigated whether there is an increase in ROS following overexpression of CYP2E1 in MCF-10A cells. We found that 30 and 100 mM EtOH increased ROS levels after 2 h treatment in CYP2E1 overexpressing cells. Based on these results and our previous studies with ROS-producing chemicals, we also examined epidermal growth factor receptor (EGFR) activation following exposure to ethanol. We found that there was an increase in phosphorylation of pY1086 EGFR after 18 h EtOH treatment in CYP2E1 overexpressing cells. These studies support a hypothesis that EtOH might increase human mammary cell activation, via an EGFR-dependent signaling mechanism associated with oxidative stress.
Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos 62209, Mexico.
Angel
A
León-Buitimea
Lourdes
L
Rodríguez-Fragoso
Fredine T
FT
Lauer
Harmony
H
Bowles
Todd A
TA
Thompson
Scott W
SW
Burchiel
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000201:enzymology / Q000378:metabolism*; D045744:Cell Line, Tumor; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D014162:Transfection
D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1; D066246:ErbB Receptors