The Hedgehog pathway is a possible therapeutic target for patients with estrogen receptor-negative breast cancer.
The Hedgehog pathway is a possible therapeutic target for patients with estrogen receptor-negative breast cancer.
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发表时间：
2009-03
影响因子：
2
通讯作者：
C. Kameda;Haruo Tanaka;A. Yamasaki;Masafumi Nakamura;Kenichiro Koga;N. Sato;M. Kubo;S. Kuroki;Masao Tanaka;M. Katano
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文献类型：
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作者：
C. Kameda;Haruo Tanaka;A. Yamasaki;Masafumi Nakamura;Kenichiro Koga;N. Sato;M. Kubo;S. Kuroki;Masao Tanaka;M. Katano
了解雌激素受体α（ER α）的表达模式对于确定乳腺癌患者的治疗策略至关重要。ER α阴性乳腺癌患者的预后仍然很差。我们以前已经表明，Hedgehog（Hh）信号在乳腺癌中被组成性激活，Hh信号可能是一个新的治疗靶点。因此，在本研究中，检查了Hh信号传导是否可以用作ER α阴性乳腺癌患者的治疗靶点。为此目的，使用三种ER α阴性乳腺癌细胞系，其中表达Hh通路相关分子，如配体Patched1和转录因子Gli1作为靶细胞。环巴胺，一种Hh通路的抑制剂，显著抑制这些癌细胞的细胞增殖和侵袭能力。此外，在这些细胞中通过RNA干扰敲低Gli1也显著降低了细胞增殖和侵袭能力。由于我们以前的数据显示，在切除的ER α阴性乳腺癌标本中，Hh通路存在组成性激活，因此Hh通路，尤其是Gli1，可能是ER α阴性乳腺癌患者的有用治疗靶点。
Understanding the expression patterns of estrogen receptor-alpha (ERalpha) is essential for determining therapeutic strategies for patients with breast cancer. The prognosis of patients with ERalpha-negative breast cancer is still poor. We have previously shown that Hedgehog (Hh) signaling is constitutively activated in breast cancer and that Hh signaling could be a new therapeutic target. Therefore, in this study, whether or not Hh signaling could be utilized as a therapeutic target for patients with ERalpha-negative breast cancer was examined. For this purpose, three ERalpha-negative breast cancer cell lines were used in which Hh pathway-related molecules such as the ligand Patched1 and the transcriptional factor Gli1 as target cells are expressed. Cyclopamine, an inhibitor of the Hh pathway, significantly suppressed both the cell proliferation and invasion ability of these cancer cells. In addition, the knockdown of Gli1 by RNA interference in these cells also significantly reduced both cell proliferation and invasion ability. Since our previous data have shown a constitutive activation of the Hh pathway in surgically-resected ERalpha-negative breast cancer specimens, the Hh pathway, especially Gli1, may be a useful therapeutic target for patients with ERalpha-negative breast cancer.