Abstract:

Objective To investigate the biological changes of normal breast epithelial cells induced byestrogen through Nrf2/ROS signaling pathway. Methods Normal breast epithelial cell lines MCF⁃10A and MCF⁃12Awere selected and the control group and estrogen group（5 nmol/L）were established. MTT assay，LDH assay，enzyme⁃linked immunosorbent assay（ELISA），DCFH⁃DA fluorescence probe labeling assay，oxidase assay，wound⁃heal⁃ing assay，colony⁃forming assay and annexinV/PI double staining were used to detect the biological characteristicsof breast cells after intervention. Expression of Nrf2，HO⁃1，NQO1 protein and mRNA in breast cells were detect⁃ed by Western blot and PCR. Results Estrogen induced the enhancement of cell viability，migration and cloningability，and reduced cell apoptosis. Estrogen induced the accumulation of ROS and inhibited the activities of SOD，GPX，CAT and TAC in the cells，and then increased the level of LDH and 8⁃OHdG in the cells，leading to theincrease of cytotoxicity and oxidative damage of DNA. In addition，Western blot and RT⁃qPCR showed that estrogeninduced inhibition of Nrf2，HO⁃1 and NQO1 expression. Conclusion Estrogen can induce the proliferation andapoptosis of normal breast cells，and regulate Nrf2/ROS signal pathway to increase the oxidative damage of DNA，and then induce the biological changes of breast cells.

Key words: estrogen, breast cancer, oxidative stress, Nrf2, ROS, 8?OHdG