title: Expression and function of survivin in canine osteosarcoma.
abstract: Osteosarcoma has a high mortality rate and remains in need of more effective therapeutic approaches. Survivin is an inhibitor of apoptosis family member protein that blocks apoptosis and drives proliferation in human cancer cells where it is commonly elevated. In this study, we illustrate the superiority of a canine osteosarcoma model as a translational tool for evaluating survivin-directed therapies, owing to the striking similarities in gross and microscopic appearance, biologic behavior, gene expression, and signaling pathway alterations. Elevated survivin expression in primary canine osteosarcoma tissue correlated with increased histologic grade and mitotic index and a decreased disease-free interval (DFI). Survivin attenuation in canine osteosarcoma cells inhibited cell-cycle progression, increased apoptosis, mitotic arrest, and chemosensitivity, and cooperated with chemotherapy to significantly improve in vivo tumor control. Our findings illustrate the utility of a canine system to more accurately model human osteosarcoma and strongly suggest that survivin-directed therapies might be highly effective in its treatment.
authors: The Animal Cancer Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523, USA.
authors: Jenette K
authors: JK
authors: Shoeneman
authors: E J
authors: EJ
authors: Ehrhart
authors: Jens C
authors: JC
authors: Eickhoff
authors: J B
authors: JB
authors: Charles
authors: Barbara E
authors: BE
authors: Powers
authors: Douglas H
authors: DH
authors: Thamm
mesh_terms: D000818:Animals; D017209:Apoptosis; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004285:Dogs; D005455:Fluorescent Antibody Technique; D020868:Gene Silencing; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism* / Q000502:physiology; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D009363:Neoplasm Proteins; D034741:RNA, Small Interfering