EphA2 overexpression decreases estrogen dependence and tamoxifen sensitivity.
EphA2 overexpression decreases estrogen dependence and tamoxifen sensitivity.
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发表时间：
2003-06
期刊：
影响因子：
11.2
通讯作者：
Ming Lu;K. Miller;Y. Gokmen-Polar;M. Jeng;M. Kinch
中科院分区：
文献类型：
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作者：
Ming Lu;K. Miller;Y. Gokmen-Polar;M. Jeng;M. Kinch
EphA2受体酪氨酸激酶在未转化的成年乳腺上皮细胞上以低水平存在，但在侵袭性乳腺癌细胞上经常过表达。最近的研究已经证明了乳腺癌细胞系中EphA2和雌激素受体表达之间的反比关系。在我们目前的研究中，我们证明EphA2的过表达降低了雌激素依赖性，如使用体外和体内标准所定义的。EphA2转染的细胞在体外表现出增加的生长，并在体内形成更大和更具侵袭性的肿瘤。EphA2过表达也降低了他莫昔芬抑制乳腺癌细胞生长和肿瘤发生的能力。EphA2过表达的这些影响可以通过基于抗体的EphA2靶向来克服。特别是，某些EphA 2抗体可以使EphA 2过表达的乳腺肿瘤细胞对他莫昔芬重新敏感。这些结果对于理解雌激素依赖的分子基础具有重要意义，并进一步证明EphA2可能为乳腺癌提供急需的治疗靶点。
The EphA2 receptor tyrosine kinase is found at low levels on nontransformed adult breast epithelial cells but is frequently overexpressed on aggressive breast cancer cells. Recent studies have documented an inverse relationship between EphA2 and estrogen receptor expression in breast cancer cell lines. In our present study, we demonstrate that overexpression of EphA2 decreases estrogen dependence as defined using both in vitro and in vivo criteria. The EphA2-transfected cells demonstrate increased growth in vitro and form larger and more aggressive tumors in vivo. EphA2 overexpression also decreases the ability of tamoxifen to inhibit breast cancer cell growth and tumorigenesis. These effects of EphA2 overexpression can be overcome by antibody-based targeting of EphA2. In particular, certain EphA2 antibodies can resensitize EphA2-overexpressing breast tumor cells to tamoxifen. These results have important implications for understanding the molecular basis underlying estrogen dependence and provide further evidence that EphA2 may provide a much-needed therapeutic target for breast cancer.