雌激素诱导的乳腺上皮细胞转化是乳腺癌发生的关键步骤。ERα选择性拮抗剂可干预这一过程，但单纯抑制ERα信号通路对ER阴性乳腺癌无效，且长期使用容易产生耐药和病情恶化，这可能与激活GPR30有关。黄芩素具有抗乳腺肿瘤的活性，我们通过分子对接发现该化合物与ERα和GPR30结构的LBD域具有较强的结合能力，提示黄芩素可能对两种受体的信号通路产生影响。在本项目中，我们通过构建雌激素诱导的细胞转化模型，考察黄芩素对这一过程的抑制作用，同时考察黄芩素对ERα表达和浆/核分布、激活ERE及其靶基因转录表达的影响，以及对GPR30的表达、GPR30介导的EGFR转活、下游ERK和Akt的活化及相关基因表达的影响，研究黄芩素能否同时通过影响ERα和GPR30两条信号通路，来干预雌激素诱导的乳腺上皮细胞转化。本项目为研究天然黄酮化合物预防乳腺癌发生提供了新的思路，具有一定的理论意义和临床应用前景。

Breast epithelium transformation induced by estrogen is the key process in breast carcinogenesis. It is confirmed that selective estrogen receptor (ERα) modulator could interfere this process, however, pure ERα antagonist is inactive to ER-negative breast cancer and long time exposure to this kind of drug conducts to occurence of breast cancer risk. Some investigations suggested that it is related to GPR30 singaling transduction. Baicalein, one flavonoid derived from the root of Scutellaria baicalensis Georgi, has been reported for its anti-cancer activity of breast cancer. Molecular modeling and binding experiments showed that there is a good affinity of the ERα and GPR30 ligand binding domian for the baicalein, which implied the potential agonist/antagonist activity of baicalein exerted through ERα and GPR30. We construct the model of transformation induced by 17β-estradiol (E2) to evaluate the effect of baicalein on transformation and the biological action exerted through ERα and GPR30. The detail molecular mechanisms analyses containing, ERα singaling including, ERα expression, cytoplasm/nucleus distribution, transactivation and gene expression induced by E2; and GPR30 singaling including, GPER-mediated EGFR, ERK/Akt activation gene transcription. In general, our project performed the investigation of baicalein on ERα and GPR30 could represent an innovative pharmacological approach targeting breast carcinomas which express one or both receptors at the beginning and/or during tumor progression.