ERβ exerts multiple stimulative effects on human breast carcinoma cells
ERβ exerts multiple stimulative effects on human breast carcinoma cells
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DOI：
10.1038/sj.onc.1207765
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发表时间：
2004-07-29
期刊：
影响因子：
8
通讯作者：
Shao, ZM
中科院分区：
文献类型：
--
作者：
Hou, YF;Yuan, ST;Shao, ZM
乳腺癌ER的最新研究表明，除了ER α外，还存在ER β。有临床资料表明ER β对乳腺癌患者的生存有预测价值，提示ER β在乳腺癌的发生、发展和转移中起着重要作用。为了验证这一假设，我们通过将人ER β cDNA重新引入MDA-MB-435细胞中来产生ER β高表达细胞系。我们证明ER β在体内和体外对人乳腺癌细胞产生多种肿瘤刺激作用。在体外研究中，ER β能够显著增加MDA-MB-435细胞的增殖和侵袭，而这些作用完全不依赖于雌二醇。此外，这种刺激的特征在于下调p2 l和上调MMP-9，以及转录因子Est-1。在体内研究中，我们还证明了ER β转染的MDA-MB-435细胞在裸鼠中比模拟或野生型细胞生长更快，并且具有更多的肺转移。在ER β转染的MDA-MB-435异种移植物中，ER β引起p21蛋白水平的显著降低。在体外研究中观察到的ER β对MMP-9和Ets-1表达的类似作用也在体内研究中观察到。这些体外和体内研究表明，ER β对乳腺癌的发展和转移具有多重促进作用。
Recent studies of ERs in breast cancer have demonstrated the existence of ERbeta in addition to ERalpha. Some clinical data indicated that ERbeta had prognostic value for patient's survival, which suggested that ERbeta plays a key role in breast cancer development and,metastasis. To test this hypothesis, we generated an ERbeta high-expression cell line by reintroduced human ERbeta cDNA into MDA-MB-435 cells. We demonstrated that ERbeta exerted multiple tumor-stimulative effects on human breast carcinoma cells both in vivo and in vitro. In in vitro studies, ERbeta was able to increase the proliferation and invasion of MDA-MB-435 cells significantly, while these effects were totally estradiol independent. Also, this stimulation was characterized by downregulation of p2l and upregulation of MMP-9, as well as transcriptional factor Est-1. In in vivo studies, we also demonstrated that ERbeta-transfected MDA-MB-435 cells grew much faster and had more pulmonary metastasis than mock or wild-type cells in nude mice. In ERbeta-transfected MDA-MB-435 xenografts, ERbeta caused significant reduction in p2l protein levels. Similar effects of ERbeta on MMP-9 and Ets-1 expression noted in vitro studies were also observed in the in vivo studies. These in vitro and in vivo studies indicated that ERbeta exerted multiple stimulative effects on breast cancer development and metastasis.