Major Highlights in the Past Year
Research
- The Newcastle team have identified the DEAD box RNA helicase, p68, as an important co-regulator of the AR.
- A major collaboration between ProMPT and the Southern Collaborative (Ros Eeles) has led to the discovery of new SNPs associated with high risk prostate cancer. The paper will be published in Nature Genetics in early February 2008.
- The Cambridge team has discovered new binding sites of the human AR in the human genome published in EMBO Reports.
- In Sheffield, OPG transcripts and proteins have been identified in stromal and cancer cells; two additional shorter splice variants have been found. Prostate cells have been engineered to stably express GFP and OPG for functional studies.
- In Manchester, lipid translocation from human bone marrow adipocytes to prostate cancer cells was found in early metastasis. Caveolin-1 was involved in this mechanism of lipid uptake. Involvement of RhoA and Rac in transmigration of prostate cancer cells across the bone marrow endothelial barrier was confirmed. Comparative genomic analysis of unexpanded stem enriched cell populations using Hoescht 33342 Side Population extractions from primary human prostate is being performed.
- In York, initial engraftment studies have established that tumour frequency is higher from a2b1 hi/CD133+ cells relative to the progenitor populations a2b1lo/CD44+ and a2b1lo/CD24+. However, only 10% of patient samples tested have resulted in tumours. An increased tumour frequency was found in the model by i) changing mouse models from NOD/SCID to Rag2-/-GC-/- transgenics and ii) expanding small biopsies of human prostate in vivo before engraftment of selected phenotypes. There is now a breeding colony of transgenic Rag2-/-GC-/- mice as an improved host for human tumour xenografts.
- In Bristol, a protocol is agreed for generating a concurrently matched, nested case-control series of prostate cancer cases and controls from men recruited to ProtecT. This case -control series currently comprises 2,036 cases and 12,782 controls, for whom extensive data (including co-morbidities, urinary and sexual symptoms, family history, diet, health and lifestyle factors) are available for analysis.
