| CHARACTERISATION
OF PEROXIREDOXIN-3 IN PROSTATE CANCER.
Dr Hayley Whitaker CRUK Cambridge Research Institute, Uro-Oncology Group |
 |
Prostate cancer is currently diagnosed using a test which detects a protein called prostate specific antigen (PSA). We can measure this protein in urine, and can determine whether a patient's treatment is working. However, PSA is not 100% accurate and so we are looking for another protein, also referred to as a "biomarker", to diagnose prostate cancer. To find new biomarkers, we look to see whether there is more or less of a particular protein in the urine, blood or tissue of people with cancer compared to people without cancer.
We are interested in studying a family of proteins called peroxiredoxin's (Prx's) as new biomarkers for prostate cancer. Prx's act like a molecular sponge, mopping up "free radicals" found in cells which can cause cancer by damaging DNA. If cells don't have enough Prx's they may be more likely to become cancerous. In total, there are six members of the Prx family called Prx1 - 6 that all mop up free radicals in a slightly different way.
Using prostate tissue from normal and cancerous areas of the prostate we have looked to see if the amount of Prx-3 had change in 32 patients. We found that the amount of Prx-3 was very low in normal tissue and that there was twice as much in the prostate cancer tissue. This suggests Prx-3 may be a good biomarker to identify prostate cancer. There is also more Prx-3 in very aggressive cancers compared to less aggressive cancers. This means that we could use Prx-3 to tell us how far a patient's cancer has developed or how they are responding to treatment.
We are also interested in why the hormone therapy that is used to treat prostate cancer often stops working. Hormones, called "androgens", are required for cancer growth and act on other proteins in the cells instructing the cells to grow, divide or spread to other organs in the body. Such proteins are said to be "androgen- regulated" and the hormone therapy that is used is termed "anti-androgen". It is difficult to investigate anti-androgens in patients; therefore, we grow a type of prostate cancer cell that has been modified to grow continuously in a culture dish. These "cell lines" can be manipulated and anti-androgens added to them to mimic prostate cancer growth and its treatment in the body.
We have treated a particular prostate cell line with anti-androgens and found that while the majority of cells died, a small number survived and continued to grow. We believe that this is similar to what happens in patients with advanced prostate cancer after hormone therapy. Therefore, we have looked at surviving cells to see how much Prx-3 is in them compared to cells that we haven't treated with drugs. There is at least three times more Prx-3 in the surviving cells, which means that Prx- 3 could be a good biomarker to monitor patients with prostate cancer so that we can tell when their cancer is progressing. We now want to try and understand what happens to cells when Prx-3 levels increase and if it has a direct effect on how cancer cells grow and spread to other parts of the body.
Progress:
The Final Report (.pdf file) is available here.
Research final report, 30 April 2008.
Project 2006/14