Prostate cancer (PCa) is driven by the androgen receptor (AR) signalling axis and begins with prostatic intraepithelial neoplasia (PIN), progressing to invasive adenocarcinoma and eventually metastatic disease. It is treated with androgen deprivation therapies, to which, in late-stage disease, tumours often become resistant and proliferation occurs in a low androgen environment. Mutation of the PTEN tumour suppressor gene is found in approximately 30% of primary human prostate adenocarcinomas and is commonly implicated in metastatic and treatment-refractory disease. In this study, transgenic murine models recapitulating the sequence of human PCa development were used, having mono- or bi-allelic PTEN deletion. Incorporation of an androgen-responsive luciferase reporter construct allowed visualisation of AR activity through bioluminescent imaging, whilst T2-weighted Magnetic Resonance Imaging (MRI) was performed to determine the effects of PTEN deletion on murine prostate pathology. In non-castrate male mice, pelvic bioluminescence was significantly greater in those with probasin-mediated prostate-specific PTEN deletion compared to age-matched controls (P=0.0285). 10, 14 and 17 month old mice heterozygous for PTEN deletion showed an age-dependent trend towards increasing pelvic bioluminescence (by bioluminescent imaging), prostatic enlargement and a greater prostate volume (by MRI imaging), while no gross structural prostate abnormalities were evident. This study demonstrates the efficacy of bioluminescent imaging to non-invasively investigate AR action in this transgenic murine model of PCa.
Funding: Prostate Cancer UK and Imperial College London
Presenting Author: Alysha Bhatti, Department of Surgery and Cancer, Imperial Centre for Translational and Experimental Medicine, Du Cane Road, W12 0NN, London, UK. Email: firstname.lastname@example.org