Johar Ramesh, Sharma Rohit, Kaur Amanpreet, Mukherjee Tapan K
Department of Biotechnology, Maharishi Markandeshwar University, Mullana, Ambala, India.
Anticancer Agents Med Chem. 2015;16(2):190-9. doi: 10.2174/1871520615666150518092315.
ROS have vital roles in cellular signaling and homeostasis. At low concentration, ROS promotes cancer cell survival by the activation of growth factors and MAP-kinases (MAPKs) that further activates cell cycle progression. At high concentration, ROS produces oxidative stress that activates programmed cell death or apoptosis. However, this fine distinction of ROS action either as a growth promoter or pro-apoptotic agent depends not only on dosage (concentration) but also on the duration, type, and site of ROS generation. The female steroid estrogens and their various metabolites generate ROS in the breast cancer cells. Slow, sustained and moderate level of ROS generated by estrogens and their metabolites cause initiation and progression of breast cancer. ROS generated by estrogens affect pro-proliferative (e.g. cyclin D1, Cdc2), prosurvival (e.g. AKT), antiapoptotic (e.g. BCl2) and pro-inflammatory (e.g. NF-κB) molecules. These multipronged actions of ROS lead to the activation of several signaling pathways involved in the breast cancer cell survival and proliferation, resulting in the progression of breast cancer. Present review article provides insights into the role of estrogen generated ROS and its associated signaling pathways in the initiation and progression of breast cancer. The importance of ROS as breast cancer drug target has also been discussed.
活性氧在细胞信号传导和内环境稳态中发挥着至关重要的作用。在低浓度时，活性氧通过激活生长因子和丝裂原活化蛋白激酶（MAPK）来促进癌细胞存活，而这些因子和激酶会进一步激活细胞周期进程。在高浓度时，活性氧会产生氧化应激，从而激活程序性细胞死亡或凋亡。然而，活性氧作为生长促进剂或促凋亡剂的这种精细区分不仅取决于剂量（浓度），还取决于活性氧产生的持续时间、类型和部位。女性甾体雌激素及其各种代谢产物在乳腺癌细胞中产生活性氧。雌激素及其代谢产物产生的缓慢、持续且适度水平的活性氧会导致乳腺癌的发生和发展。雌激素产生的活性氧会影响促增殖分子（如细胞周期蛋白D1、细胞周期蛋白依赖性激酶2）、促存活分子（如蛋白激酶B）、抗凋亡分子（如B细胞淋巴瘤2）和促炎分子（如核因子κB）。活性氧的这些多方面作用会导致参与乳腺癌细胞存活和增殖的多种信号通路被激活，从而导致乳腺癌的进展。本综述文章深入探讨了雌激素产生的活性氧及其相关信号通路在乳腺癌发生和发展中的作用。还讨论了活性氧作为乳腺癌药物靶点的重要性。
