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3‐Phosphoinositide‐dependent protein kinase‐1/Akt signalling and inhibition in a canine prostate carcinoma cell line
Author(s) -
Alvarez F. J.,
Murahari S.,
Couto C. G.,
Rosol T. J.,
Kulp S. K.,
Chen C.S.,
Kisseberth W. C.
Publication year - 2007
Publication title -
veterinary and comparative oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 34
eISSN - 1476-5829
pISSN - 1476-5810
DOI - 10.1111/j.1476-5829.2006.00117.x
Subject(s) - protein kinase b , pi3k/akt/mtor pathway , prostate cancer , cancer research , gsk 3 , phosphorylation , prostate , signal transduction , kinase , chemistry , medicine , biology , endocrinology , cancer , microbiology and biotechnology
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.