Wang Yongchao, Xu Mei, Ke Zun-Ji, Luo Jia
Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536, United States.
Department of Biochemistry, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Pharmacol Res. 2017 Jan;115:299-308. doi: 10.1016/j.phrs.2016.12.005. Epub 2016 Dec 8.
Breast cancer is a leading cause of morbidity and mortality in women. Both Epidemiological and experimental studies indicate a positive correlation between alcohol consumption and the risk of breast cancer. While alcohol exposure may promote the carcinogenesis or onset of breast cancer, it may as well enhance the progression and aggressiveness of existing mammary tumors. Recent progress in this line of research suggests that alcohol exposure is associated with invasive breast cancer and promotes the growth and metastasis of mammary tumors. There are multiple potential mechanisms involved in alcohol-stimulated progression and aggressiveness of breast cancer. Alcohol may increase the mobility of cancer cells by inducing cytoskeleton reorganization and enhancing the cancer cell invasion by causing degradation and reconstruction of the extracellular matrix (ECM). Moreover, alcohol may promote the epithelial-mesenchymal transition (EMT), a hallmark of malignancy, and impair endothelial integrity, thereby increasing the dissemination of breast cancer cells and facilitating metastasis. Furthermore, alcohol may stimulate tumor angiogenesis through the activation of cytokines and chemokines which promotes tumor growth. Additionally, alcohol may increase the cancer stem cell population which affects neoplastic cell behavior, aggressiveness, and the therapeutic response. Alcohol can be metabolized in the mammary tissues and breast cancer cells which produces reactive oxygen species (ROS), causing oxidative stress. Recent studies suggest that the epidermal growth factor receptor (EGFR) family, particularly ErbB2 (a member of this family), is involved in alcohol-mediated tumor promotion. Breast cancer cells or mammary epithelial cells over-expressing ErbB2 are more sensitive to alcohol's tumor promoting effects. There is considerable cross-talk between oxidative stress and EGFR/ErbB2 signaling. This review further discusses how the interaction between oxidative stress and EGFR/ErbB2 signaling contributes to the cellular and molecular events associated with breast cancer aggressiveness. We also discuss the potential therapeutic approaches for cancer patients who drink alcoholic beverages.
乳腺癌是女性发病和死亡的主要原因。流行病学和实验研究均表明，饮酒与患乳腺癌风险之间存在正相关。虽然酒精暴露可能促进乳腺癌的致癌作用或发病，但它也可能增强现有乳腺肿瘤的进展和侵袭性。这一研究领域的最新进展表明，酒精暴露与浸润性乳腺癌相关，并促进乳腺肿瘤的生长和转移。酒精刺激乳腺癌进展和侵袭性涉及多种潜在机制。酒精可能通过诱导细胞骨架重组增加癌细胞的迁移能力，并通过引起细胞外基质（ECM）的降解和重建增强癌细胞的侵袭。此外，酒精可能促进上皮-间质转化（EMT），这是恶性肿瘤的一个标志，并损害内皮完整性，从而增加乳腺癌细胞的扩散并促进转移。此外，酒精可能通过激活促进肿瘤生长的细胞因子和趋化因子来刺激肿瘤血管生成。另外，酒精可能增加癌症干细胞群体，这会影响肿瘤细胞行为、侵袭性和治疗反应。酒精可在乳腺组织和乳腺癌细胞中代谢，产生活性氧（ROS），导致氧化应激。最近的研究表明，表皮生长因子受体（EGFR）家族，特别是ErbB2（该家族的一员），参与酒精介导的肿瘤促进作用。过表达ErbB2的乳腺癌细胞或乳腺上皮细胞对酒精的肿瘤促进作用更敏感。氧化应激与EGFR/ErbB2信号传导之间存在大量相互作用。本综述进一步讨论了氧化应激与EGFR/ErbB2信号传导之间的相互作用如何促成与乳腺癌侵袭性相关的细胞和分子事件。我们还讨论了饮酒的癌症患者的潜在治疗方法。
