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HSP70 Inhibition in Canine Osteosarcoma Cell Lines

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Title: HSP70 Inhibition in Canine Osteosarcoma Cell Lines
Author: Asling, Jonathan
Department: Department of Biomedical Sciences
Program: Biomedical Sciences
Advisor: Mutsaers, Anthony
Abstract: Osteosarcoma (OSA) is the most common primary bone cancer in canines. Despite the ability of chemotherapy treatment to prolong survival, canine patients continue to have a poor long term prognosis. Heat shock proteins (HSPs) typically function as molecular chaperones. Under stressful conditions, HSPs can prevent apoptosis. The presence of HSP70 is related to the development of grade III lesions and the absence of HSP70 is associated with longer survival times in canines. Treatment of canine OSA cell lines with VER155008, an N-terminal ATPase inhibitor of HSP70, induced apoptosis and decreased the number of colonies formed in clonogenic survival assays. However, in response to HSP70 inhibition, canine OSA cells up-regulate HSP70 and its protein family member GRP78. Up-regulation of HSP70 was not reliant upon AKT activity, while GRP78 over expression is likely driven by the unfolded protein response. Given the role of HSP70 and GRP78 in the prevention of apoptosis, further studies are required to determine if their expression patterns are detrimental to apoptosis induction.
URI: http://hdl.handle.net/10214/8457
Date: 2014-08
Rights: Attribution-NonCommercial 2.5 Canada
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Attribution-NonCommercial 2.5 Canada Except where otherwise noted, this item's license is described as Attribution-NonCommercial 2.5 Canada