Mice to Men - Prostate cancer and PTEN.

Prostate cancer is the second most common cancer in the UK, and the second most lethal cancer in men. Treatment of prostate cancer is challenging because clinically similar tumours give rise to diverse clinical outcomes, and there are no reliable markers to discriminate benign from aggressive tumours. We study PTEN, which is lost in 40-80% of prostate tumours, and is correlated with disease severity. Biochemically, PTEN dephosphorylates phosphatidylinositol 3,4,5-trisphosphate (PIP3) to produce phosphatidylinositol 4,5-trisphosphate (PIP2). This opposes signalling through the AKT/MTOR pathway, which is a key regulator of cell growth, division and survival. However, the identity and significance of other pathways that are controlled by PTEN are unknown. Our lab has developed a mutant of PTEN (Y138L), which is able to control AKT signalling, but which is unable to regulate other signalling pathways that are normally controlled by PTEN. In the current work, we have bred mice with prostate specific changes in PTEN to investigate the relative importance of AKT independent signalling in the development of prostate cancer.