Prostate cancer developmental therapies that inhibit insulin-like growth factor’s (IGF-1) from activating its target receptor could have unexpected results especially if p53 is already compromised, according to investigators at Fred Hutchinson Cancer Research Center.
IGF-1 is a polypeptide hormone that can influence growth, differentiation, and survival of cells expressing the type 1 receptor (IGF-1R). Past studies have strongly implicated IGF-1 as a contributing factor in prostate cancer, including linking elevated levels of IGF-1 with the risk of developing this disease.
Through manipulation of gene expression in the epithelial compartment of the mouse prostate gland, researchers found that eliminating IGF-1R expression in an otherwise normal mouse prostate caused the cells to proliferate and become hyperplastic. Persistent loss of IGF-1R expression, however, ultimately induced cell stasis and death, both of which are regulated by the tumor suppressor gene p53.
The team then conducted a second experiment by crossing mice carrying the prostate-specific IGF-1R knockout alleles with transgenic mice that develop spontaneous prostate cancer when p53 is compromised. The results showed that prostate epithelial-specific deletion of IGF-1R facilitated the emergence of aggressive prostate cancer in the tumor-prone mice.
The study is published in the May 1 edition of Cancer Research.