Novel link between estrogen receptor α and hedgehog pathway in breast cancer
Novel link between estrogen receptor α and hedgehog pathway in breast cancer
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发表时间：
2008-03
影响因子：
2
通讯作者：
Kenichiro Koga;Masafumi Nakamura;H. Nakashima;Takashi Akiyoshi;M. Kubo;N. Sato;S. Kuroki;M. Nomura;Masao Tanaka;M. Katano
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文献类型：
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作者：
Kenichiro Koga;Masafumi Nakamura;H. Nakashima;Takashi Akiyoshi;M. Kubo;N. Sato;S. Kuroki;M. Nomura;Masao Tanaka;M. Katano
配体依赖性的刺猬（Hh）通路的组成性激活在包括乳腺癌在内的各种癌症的发展中是重要的。本文首次揭示了人类乳腺癌中雌激素受体α（ERα）与Hh通路之间的联系。在ERα阳性细胞中，雌激素耗竭降低了Hh通路的配体Sonic Hedgehog（Shh）的表达，而雌激素补充则引发Shh上调。这种雌激素诱导的Shh表达以配体依赖性方式激活Hh通路，并增加细胞增殖。这些作用被ERα抑制剂抑制，包括ICI 182，780（ICI），ERα的显性负性形式和针对ERα的小干扰RNA（siRNA）。与体外实验结果一致，ERα和Shh在乳腺癌组织中的表达呈正相关。这些数据表明，ERα通过Shh诱导调节Hh通路，并促进乳腺癌的发展。
Ligand-dependent constitutive activation of the hedgehog (Hh) pathway is important in the development of various carcinomas including breast cancer. A link between estrogen receptor α (ERα) and the Hh pathway in human breast cancer is shown here for the first time. In ERα- positive cells, estrogen depletion decreased the expression of sonic hedgehog (Shh), a ligand of the Hh pathway, while estrogen supplementation triggered Shh up-regulation. This estrogen-induced Shh expression activated the Hh pathway in a ligand-dependent manner, and increased cell proliferation. These effects were suppressed by ERα inhibitors, including ICI 182,780 (ICI), the dominant negative form of ERα and small interfering RNA (siRNA) against ERα. Consistent with the in vitro data, a positive correlation between ERα and Shh expression was found in breast cancer tissues. These data suggest that ERα regulates the Hh pathway through Shh induction, and promotes breast cancer development.