| PROTEOLYSIS
INDUCING FACTOR AS A SURVIVAL AND PROLIFERATION FACTOR IN PROSTATIC
CARCINOMA CELLS AND ITS POTENTIAL AS A FUTURE THERAPEUTIC TARGET.
Mr Grant D Stewart, Mr Antony Riddick, Mr S Alan McNeill, Professor Kenneth C H Fearon, Dr Fouad K Habib and Dr James A Ross The Prostate Research Group and Department of Urology, Tissue Injury and Repair Group, University of Edinburgh |
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Since taking up this grant from the Prostate Research Campaign UK in May 2006 progress on this project has been excellent. Previously research has demonstrated that prostate cancer cells can produce a molecule known as proteolysis-inducing factor (PIF). PIF is known to be responsible for weight loss in patients with advanced cancers. However, it has been established that the gene from which PIF is derived is a cancer causing gene in advanced breast cancer cells. Additionally, PIF appears to allow the survival of breast cancer cells as well as nerve cells when they are subjected to free radicals that exist in our daily environments.
Over the past few months we have been able to confirm the production of PIF by some prostate cancer cells. Following on from this we have genetically modified a prostate cancer cell to produce PIF in large quantities. By comparing the response of the PIF overproducing cell with prostate cancer cells unable to produce PIF we have been able to investigate the role of PIF on the survival of prostate cancer cells.
Figure 1. Effect of PIF production on prostate cancer cell growth.
We have been able to show that prostate cancer cells which overproduce PIF are able to grow faster than those that do not produce PIF (figure 1). Further experiments have shown that when cells overproducing PIF are subjected to stress by oxygen free radicals, a situation common in prostate cancers, they are able to survive this insult more easily that cells which are not able to express PIF (figure 2). Special cell staining techniques have shown us that the overproduction of PIF prevents cell death by a combination of two separate mechanisms, known as necrosis and apoptosis. We have also shown that PIF production prevents cancer cell death when they are subjected to low oxygen conditions, also common in prostate cancer. The results of these experiments are being prepared for publication and are being presented at a Surgical Scientific Meeting in Hong Kong, October 2006.
Figure 2. Effect of PIF production on cells stressed with free radicals.
We have started experiments to determine which part of the PIF molecule is responsible for the protective effect outlined above. We have additional work ongoing looking further into the production of PIF in prostate cancer cells taken from men with the disease. This will inform of us how commonly PIF is expressed by prostate cancer and which part of the molecule we should target as a future target in its treatment.
Interim research report dated 20 November 2006
Project 2005/04