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. This project will provide broad training in cell and molecular biology. Depending on progress, there may be opportunities to become adept in primary/explant culture, genome editing and transcriptional and phospho-proteomic profiling

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