title: Hedgehog signaling is activated in canine transitional cell carcinoma and contributes to cell proliferation and survival.
abstract: Transitional cell carcinoma (TCC) is the most commonly diagnosed tumor of the canine urinary system. Hedgehog (HH) signaling represents one possible novel therapeutic target, based on its recently identified central role in human urothelial carcinoma. The purpose of this study was to determine if HH mediators are expressed in canine TCC and the effect of inhibition of this pathway on cell growth and survival. HH pathway mediators were found to be expressed in five canine TCC cell lines. Indian HH was expressed in tumor cells in five canine bladder tumor tissues, but not in normal canine bladder tissue. Inhibition of HH signaling with cyclopamine and GANT61 led to significantly decreased cell proliferation but had a smaller effect on apoptosis. These results support future investigation of inhibitors of HH signaling in the treatment of canine TCC.
authors: Colorado State University, Animal Cancer Center, Fort Collins, CO, USA.
authors: T L
authors: TL
authors: Gustafson
authors: VCA Veterinary Care Animal Hospital and Referral Center, Oncology, Albuquerque, NM, USA.
authors: B E
authors: BE
authors: Kitchell
authors: Colorado State University, CVMBS-VTH, Animal Cancer Center, Fort Collins, CO, USA.
authors: B
authors: B
authors: Biller
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000235:genetics / Q000662:veterinary*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004283:Dog Diseases / Q000188:drug therapy / Q000235:genetics*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D053823:Hedgehog Proteins / Q000187:drug effects* / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000662:veterinary; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000662:veterinary*; D014704:Veratrum Alkaloids / Q000494:pharmacology
chemical_list: C551027:GANT 61; D053823:Hedgehog Proteins; D011725:Pyridines; D011743:Pyrimidines; D014704:Veratrum Alkaloids; C000541:cyclopamine
keywords: Hedgehog; transitional cell carcinoma