IGF‐1 and Prostate Cancer

By virtue of their potent proliferative and anti-apoptotic effects, the insulin-like growth factors (IGFs) have been the subject of long-term scrutiny for their role in tumorigenesis. With regard to prostate cancer in particular, IGF-1 has been shown to stimulate the proliferation of human prostate epithelial cells in culture and to be necessary for normal growth and development of the rat and mouse prostate. Epidemiological studies have established a link between high circulating serum IGF-1 levels and the risk of later developing advanced prostate cancer, and overexpression of IGF-1 in the prostate basal epithelial layer of transgenic mice results in prostate adenocarcinoma that is similar to human disease. Thus, IGF-1 action appears to be important for prostate cancer initiation. On the other hand, decreased IGF action, subsequent to the down-regulation of IGF-1 receptor expression, is associated with advanced, metastatic disease. This decrease in IGF-1 receptor may confer a survival advantage to prostate cancer cells that have entered the circulation by making them resistant to the differentiative effects of IGF-1 at metastatic sites such as bone. The molecular mechanisms that effect IGF-1 receptor down-regulation appear to involve novel oncogenic functions of the Wilms' tumour suppressor, as well as novel actions of the androgen receptor.