1Department of Pathology and 2Department of Obstetrics and Gynecology

D ow nloaded from Aberrant activation of Hedgehog pathway has been implicated in the development of human malignancies. This study aimed at investigating the role of hedgehog molecules in human ovarian carcinogenesis. The expression profiles of hedgehog molecules were examined in ovarian tumor samples and ovarian cancer cell lines and the in vitro effects of hedgehog molecules on cell proliferation, apoptosis, migration, invasion and cell differentiation as well as related downstream target genes were assessed. Overexpression of Patched and Gli1 protein in ovarian cancers correlated with poor survival of the patients (P=0.008; P=0.004). Significantly elevated expression of Shh mRNA was observed in ovarian cancers compared with normal tissues and benign ovarian tumors and such differential expression was specific to histological types (P<0.05). Ectopic Gli1 overexpression in ovarian cancer cells conferred increased cell proliferation, cell mobility, invasiveness and change in differentiation in association with increased expression of E-cadherin, vimentin, Bcl-2, caspases as well as β1 integrin, membrane type 1 matrix metalloproteinase (MT1-MMP), and vascular endothelial growth factor (VEGF). Treatment with KAAD-cyclopamine induced cancer cell apoptosis, suppressed cell growth, mobility and invasiveness, and induced cancer cell de-differentiation with decreased expression of E-cadherin, cytokeratin 7