Abstract
Understanding the expression patterns of estrogen receptor-α (ERα) is essential for determining therapeutic strategies for patients with breast cancer. The prognosis of patients with ERα-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 ERα-negative breast cancer was examined. For this purpose, three ERα-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 ERα-negative breast cancer specimens, the Hh pathway, especially Gli1, may be a useful therapeutic target for patients with ERα-negative breast cancer.
- Received May 28, 2008.
- Revision received August 20, 2008.
- Accepted September 29, 2008.
- Copyright© 2009 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved