FRIDAY, May 2 (HealthDay News) -- Work with a knockout mouse model points to a crucial role for insulin-like growth factor type I receptor (IGF-IR) signaling in prostate cancer and a growth control mechanism dependent upon IGF-IR, according to research published in the May 1 issue of Cancer Research.
Brent W. Sutherland, Ph.D., of the Fred Hutchinson Cancer Research Center in Seattle, and colleagues describe their work with IGF-IRloxP/loxP;ARR2PBi-Cre (IGF-IR knockout mice), IGF-IR titrated mice and IGF-IR intact control mice. They found that conditional deletion of IGF-IR leads to hyperplasia in lateral, ventral and dorsal prostate lobes, and proliferation in these lobes and the anterior lobe.
In addition, conditional deletion of IGF-IR creates age-dependent apoptosis and senescence and can increase ERK1/2 activation in the dorsal and lateral lobes. The research also points to a p53-dependent cell-specific link between IGF-IR loss and repression of phosphorylated Akt and p44/42 in the ventral prostate and activation of p44/42 in the dorsal prostate. Finally, in a p53 depletion-dependent model of multistage tumorigenesis, conditional deletion of IGF-IR doesn't inhibit progressive cancer, the authors write.
"In summary, genetically engineered mouse models are helping us to define a new paradigm for IGF-I action in the prostate gland that should further help guide translational initiatives to target the IGF-I axis in prostate and other cancers using small-molecule inhibitors and other therapeutic strategies," the authors conclude.
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