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- Title
3-Phosphoinositide-dependent protein kinase-1/Akt signalling and inhibition in a canine prostate carcinoma cell line.
- Authors
Alvarez, F. J.; Murahari, S.; Couto, C. G.; Rosol, T. J.; Kulp, S. K.; Chen, C.-S.; Kisseberth, W. C.
- Abstract
Deregulation of the 3-phosphoinositide-dependent protein kinase-1 (PDK-1)/Akt signalling pathway is associated with prostate cancer development and progression. Inhibition of PDK-1/Akt signalling can be achieved using structurally optimized celecoxib derivatives such as OSU-03012. In this study, we treated the novel canine prostate cancer cell line, Ace-1, with OSU-03012 or dimethyl sulphoxide in vitro. We found that Akt was constitutively phosphorylated in the canine prostate cancer cell line Ace-1 and that there was a dose-dependent decrease in cell viability, and Akt and glycogen synthase kinase-3β phosphorylation, in response to OSU-03012 treatment. This was accompanied by a dose-dependent increase in apoptosis. These data suggest that Akt signalling pathway inhibition is a potential strategy for the treatment of dogs with prostate cancer and that canine prostate cancer is a relevant large animal model for evaluating Akt pathway inhibitors such as OSU-03012 for use in people.
- Subjects
PHOSPHOINOSITIDES; PROTEIN kinases; PROSTATE cancer; CANCER cells; LABORATORY dogs; VETERINARY oncology
- Publication
Veterinary & Comparative Oncology, 2007, Vol 5, Issue 1, p47
- ISSN
1476-5810
- Publication type
Article
- DOI
10.1111/j.1476-5829.2006.00117.x