雌激素受体（ER）阴性乳腺癌是恶性程度最高的乳腺癌类型，目前其发生转移的机制尚未阐明。近年来研究发现新型雌激素受体GPR30与ER（-）乳腺癌的增殖和侵袭密切相关，而经典雌激素受体ERβ在ER（-）乳腺癌中存在表达，且与肿瘤恶性程度密切相关。我们新近发现在ER（-）乳腺癌细胞株SKBR-3和MDA-MB-231中GPR30与ERβ呈不同程度的表达；在MDA-MB-231细胞中同时激活GPR30和ERβ途径可下调ERβ的表达，且抑制ERβ途径诱导的癌细胞迁移和侵袭。故我们提出假设：雌激素促进ER（-）乳腺癌转移可能与GPR30和ERβ功能拮抗现象有关。本项目拟通过：（1）检测病理标本及建立荷瘤小鼠模型明确GPR30、ERβ与乳腺癌进展的关系；（2）采用DNA测序等方法研究GPR30与ERβ功能拮抗现象，探讨雌激素促进ER（-）乳腺癌转移的分子机制，为防治ER（-）乳腺癌转移提供新的分子靶点。

Estrogen receptor negative breast cancer is the most malignancy breast cancer subtype. However the underline mechanisms induce its metastasis are poorly elucidate by now. During recent years, a neotyte estrogen receptor GPR30 have been detected in the ER-negative breast cancer cell and several study had suggested its functions are closely associated with ER(-) breast cancer proliferation and invasion, and ERβ also has a certain expression in breast cancer, and is closely related to the tumor malignant degree. Our previous study found that in the ER (-) breast cancer ER-negative breast cancer cell lines SKBR-3 and MDA-MB-231, the expression of GPR30 and ERβ in varying degrees, when activated two receptors at the same time reduced the expression of ERβ. Base on these works, we hypothesis that: estrogen may promote ER-negative breast cancer metastasis via the antagonism of GPR30 and ERβ. In order to test this hypothesis, we plan to study: 1、through clinical specimens and animal model evaluate the relationship between GPR30、ERβ and ER-negative breast cancer. 2、DNA sequencing and co-immunoprecipitation are applied to ascertain the antagonism of GPR30 and ERβ.This research would reveal a new mechanism of ER-negative breast cancer metastasis and found that GPR30 and ERβ play an important role in it. Our study may provide a new molecular target for control ER-negative breast cancer metastasis.