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IDENTIFICATION OF A PUTATIVE TUMOUR SUPPRESSOR IN PROSTATE CANCER.

Dr Tahereh Kamalati

Imperial College London, Department of Oncology

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Background:
The majority of prostate tumours arise from prostate epithelial cells. We have developed "tools" for studying the cell surface of human prostate epithelial cells in order to better understand prostate cancer development and progression, with specific view to development of new diagnostic and therapeutic approaches. One of our "tools" detects a protein present in abundance on the cell surface of normal prostate epithelial cells. Importantly, this protein is lost from the cell surface of prostate cancer cells. Our results indicate that our "tool" is detecting a protein whose loss causes cancer. This type of protein is called Tumour Suppressor. We propose to identify this tumour suppressor by virtue of the fact that our "tool" can react with it directly. Once we have identified the tumour suppressor, we aim to examine how loss of this tumour suppressor helps prostate cancer cell growth, tumour formation and metastasis. Ultimately, we aim to develop our "tool" as a new diagnostic for prostate cancer.

Aim:
The "tools" we have generated are called "antibodies". The reason we have made antibodies as tools is that antibodies are naturally occurring proteins, which are made by the human body as a part of its defence system. We have already established that the target for our antibody is not one of the known prostate cell surface proteins previously reported. Because we have an antibody that binds the tumour suppressor directly and strongly, as the first step in our investigations, we aim to use our antibody to extract the tumour suppressor from the surface of the cells. Once we have purified the tumour suppressor, we aim to examine its chemical composition and determine its identity. Additionally, we aim to establish the tissue distribution of this tumour suppressor in normal human organs as well as tumours arising from organs other than prostate.

How long it will take?
Our proposed investigation will take one year.

What are the expected outcomes?
The expected result from this proposal is the identification of a novel tumour suppressor in prostate cancer together with elucidations of its tissue distribution in normal organs and tumours other than prostate. Collectively, the results generated in this study will facilitate future genetic engineering studies to establish the functional mechanism by which this tumour suppressor prevents tumour formation and growth in human prostate epithelial cells. Ultimately, we aim to use this antibody in the development of new strategies for prostate cancer therapy and diagnosis.

How could it make a difference to men's lives?
We have developed a tool, which reacts with a tumour suppressor in human prostate cancer. This proposal aims to identify the tumour suppressor and ultimately elucidate its mechanism of action. Hence, the findings of this project could lead to a better understanding of prostate cancer development, tumour formation and tumour metastasis. Additionally, our findings will lead to development of novel diagnostic and therapeutic approaches for the treatment of prostate cancer.

Research summary, 25 March 2008.
Project 2007/11