OBJECTIVE: We investigated the expression and function of the hedgehog (Hh) pathway in human esophageal squamous cell carcinoma (ESCC). METHODS: The expression of Hh pathway molecules were detected in 34 human ESCC cell lines by RT-PCR. Subsequently, we investigated the effects of cyclopamine, a specific inhibitor of the Hh pathway, on cell proliferation, migration and invasion. Next, the effects of siRNA targeting Gli-1 were examined. Immunohistochemically, the expression of Gli-1 was studied in 104 ESCC specimens and compared with the clinicopathological characteristics of the patients. RESULTS: Gli-1 were expressed in 31 of 34 cell lines (91%), while Sonic hedgehog (SHh), Patched (Ptch), and Smoothened (Smo) expression was noted in all 34 cell lines. Cyclopamine significantly inhibited cell proliferation and migration in ESCC cells that expressed Gli-1. siRNA targeting Gli-1 inhibited cell growth in ESCC cells. Gli-1 was expressed in 52 of 104 cancer specimens (50%). Gli-1 expression was associated with tumor depth (p < 0.001), positive lymph node metastasis (p = 0.004) and a poor prognosis (p = 0.0047). CONCLUSION: Our results raise the possibility that the inhibition of the Hh pathway could be a novel target for esophageal cancer therapy. Copyright 2006 S. Karger AG, Basel.
OBJECTIVE: We investigated the expression and function of the hedgehog (Hh) pathway in humanesophageal squamous cell carcinoma (ESCC). METHODS: The expression of Hh pathway molecules were detected in 34 human ESCC cell lines by RT-PCR. Subsequently, we investigated the effects of cyclopamine, a specific inhibitor of the Hh pathway, on cell proliferation, migration and invasion. Next, the effects of siRNA targeting Gli-1 were examined. Immunohistochemically, the expression of Gli-1 was studied in 104 ESCC specimens and compared with the clinicopathological characteristics of the patients. RESULTS:Gli-1 were expressed in 31 of 34 cell lines (91%), while Sonic hedgehog (SHh), Patched (Ptch), and Smoothened (Smo) expression was noted in all 34 cell lines. Cyclopamine significantly inhibited cell proliferation and migration in ESCC cells that expressed Gli-1. siRNA targeting Gli-1 inhibited cell growth in ESCC cells. Gli-1 was expressed in 52 of 104 cancer specimens (50%). Gli-1 expression was associated with tumor depth (p < 0.001), positive lymph node metastasis (p = 0.004) and a poor prognosis (p = 0.0047). CONCLUSION: Our results raise the possibility that the inhibition of the Hh pathway could be a novel target for esophageal cancer therapy. Copyright 2006 S. Karger AG, Basel.
Authors: Christine H Chung; James J Dignam; M Elizabeth Hammond; Alexander C Klimowicz; Stephanie K Petrillo; Anthony Magliocco; Richard Jordan; Andy Trotti; Sharon Spencer; Jay S Cooper; Quynh-Thu Le; K Kian Ang Journal: J Clin Oncol Date: 2011-02-28 Impact factor: 44.544