Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos 62209, Mexico.
Toxicol Lett. 2012 Mar 7;209(2):161-5. doi: 10.1016/j.toxlet.2011.12.009. Epub 2011 Dec 28.
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.
乳腺癌是最常见的癌症，也是全球癌症相关死亡的第二大主要原因。乳腺癌的病因非常多样化，乙醇（EtOH）的摄入是女性患乳腺癌的一个明确的危险因素。然而，乙醇在乳腺组织中发挥致癌活性的机制尚不清楚。CYP2E1 已知能代谢乙醇并产生活性氧（ROS），包括上皮细胞中的超氧自由基。因此，在本研究中，我们研究了 CYP2E1 在 MCF-10A 细胞中过表达后是否会增加 ROS。我们发现，30 和 100 mM EtOH 在 CYP2E1 过表达细胞中处理 2 小时后增加了 ROS 水平。基于这些结果和我们之前对产生 ROS 的化学物质的研究，我们还检查了乙醇暴露后表皮生长因子受体（EGFR）的激活。我们发现，CYP2E1 过表达细胞中，经过 18 小时 EtOH 处理后，pY1086 EGFR 的磷酸化增加。这些研究支持了一种假说，即乙醇可能通过与氧化应激相关的 EGFR 依赖的信号机制增加人乳腺细胞的激活。
