ER和HER2/PI3K-AKT信号转导通路间的交叉对话与乳腺组织癌变最密切相关。前期研究证实乳岩内消霜外用对乳腺癌前病变具有良好的治疗作用，可显著降低癌前病变组织细胞ERα、p-Akt、HER2蛋白、PIK3CAmRNA的水平，升高PTEN蛋白及mRNA的水平，提示其良好疗效与干预该两条通路密切相关。本项目通过DMBA联合雌孕激素序贯诱导动物模型，采用免疫印迹、液质联用、流式细胞术等，检测该两条信号通路关键分子ER-α36、ER-α66、HER2、Bcl-2、cyclinD1等的变化水平，明晰ER与HER2/PI3K-AKT信号通路间交叉对话机制及介导该霜调节两通路交叉对话的关键信号分子。并利用MCF-10AT细胞模型，阻断或沉默关键信号分子进行确证。此研究可进一步揭示乳腺癌前病变发生、发展的核心机制，及乳岩内消霜外用有效治疗乳腺癌前病变和预防、阻断乳腺癌发生发展的作用机理甚至作用靶点。

The cross-talk between ER and HER2/PI3K-AKT signal transduction pathways is most closely related to breast carcinogenesis. Preliminary studies confirm that Ruyanneixiao has good therapeutic effect on breast precancerous lesion. It can significantly reduce the protein levels of ERα, HER2 and p-Akt, and PIK3CAmRNA level. Also, it can increase the protein level and mRNA level of PTEN in the precancerous lesion tissue. Suggesting its good efficacy is closely related to intervention ER and HER2/PI3K-AKT pathways. This project detects the key molecules ER-α36、ER-α66、HER2、Bcl-2、cyclinD1, etc in these two signaling pathways on animal models induced by 7, 12-Dimethylbenz[a]anthracen combined estrogen and progesterone by Western blot, LC-MS and FCM technology. To analysis the cross-talk mechanism of ER and HER2/PI3K-AKT signaling pathways, to clear the effect mechanism of Ruyanneixiao and to confirm it by blocking or silencing the key signaling molecules. This study may further clarify breast precancerous lesions pathogenesis and reveals Ruyanneixiao effect mechanism.