Cortez V, Mann M, Brann D W, Vadlamudi R K
Department of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio TX 78229, USA.
Minerva Ginecol. 2010 Dec;62(6):573-83.
The estrogen receptor (ERa) is implicated in the progression of breast cancer. Hormonal therapies which block ER functions or local and systemic estrogen production are currently used to treat ERa positive breast cancer. Hormonal therapy shows beneficial effects, however, initial or acquired resistance to endocrine therapies frequently occurs, and tumors recur as metastasis. Emerging evidence suggests in addition to exerting its well-studied nuclear functions, ERa also participates in extranuclear signaling that involve growth factor signaling components, adaptor molecules and the stimulation of cytosolic kinases. ERa extranuclear pathways have the potential to activate gene transcription, modulate cytoskeleton, and promote tumor cell proliferation, survival, and metastasis. Cytoplasmic/membrane ERa is detected in a subset of breast tumors and expression of extranuclear components ERa is deregulated in tumors. The extranuclear actions of ER are emerging as important targets for tumorigenic and metastatic control. Inhibition of ERa extranuclear actions has the potential to prevent breast tumor progression and may be useful in preventing ERa positive metastasis. In this review, we summarize the results of recent research into the role of ERa mediated extranuclear actions in breast tumorigenesis and metastasis.
雌激素受体（ERα）与乳腺癌的进展有关。目前，阻断ER功能或局部及全身雌激素生成的激素疗法被用于治疗ERα阳性乳腺癌。激素疗法显示出有益效果，然而，内分泌疗法的初始或获得性耐药经常发生，肿瘤会以转移的形式复发。新出现的证据表明，除了发挥其经过充分研究的核功能外，ERα还参与涉及生长因子信号成分、衔接分子和细胞溶质激酶刺激的核外信号传导。ERα核外途径有可能激活基因转录、调节细胞骨架，并促进肿瘤细胞增殖、存活和转移。在一部分乳腺肿瘤中可检测到细胞质/膜ERα，且肿瘤中核外成分ERα的表达失调。ER的核外作用正成为肿瘤发生和转移控制的重要靶点。抑制ERα的核外作用有可能预防乳腺肿瘤进展，可能对预防ERα阳性转移有用。在本综述中，我们总结了近期关于ERα介导的核外作用在乳腺肿瘤发生和转移中的作用的研究结果。
