Investigating the Contribution of IGF-1 to Risk of Developing Prostate Cancer
Subjects with low circulating insulin-like growth factor-1 (IGF-1) are strongly protected from cancer, while men with high IGF-1 are at increased risk of prostate cancer. IGFs are also implicated in the association of tall height with aggressive, lethal prostate cancer. Experimental data suggest this is a causative association. We recently found that high serum IGF-1 associates with altered expression/localisation of IGF receptor (IGF-1R) in malignant prostatic epithelium. This project will investigate the hypothesis that high IGF-1 signals via IGF-1R to promote growth of occult tumours so they become clinically significant. Using cell lines, primary cultures and clinical tissues, the student will investigate: 1) whether manipulation of IGF-1 supply affects IGF-1R expression, localisation and downstream signalling in benign or malignant prostate; 2) whether IGF response varies with genotype including PTEN, AR-V7 and TMPRSS2-ERG status; 3) the functional significance of IGF-1R effectors identified as candidate mediators of high IGF-1. The long-term aims are to understand how high serum IGF-1 promotes cancer risk and progression, and develop new approaches to risk reduction.