| MODULATION OF PROTEIN EXPRESSION
BY CONJUGATED LINOLEIC ACID (CLA) IN PROSTATE CANCER CELLS
Mrs Pam Barker*, Dr Andrew C Schofield*, Prof Klaus WJ Wahle**, Prof Steven D Heys*. * Department of Surgery, University of Aberdeen |
Introduction
Prostate cancer has become one of the most commonly diagnosed cancers in men. It accounts for 17% of all new cases of cancer in the UK and is the second leading cause of death from malignant disease. Little is known about its aetiology, although over the last few decades, it has become increasingly evident that dietary factors play a major part in the biological processes related to prostatic carcinogenesis. From in vitro studies on human cancer cell lines and animal studies, it is clear that certain dietary fatty acids exert inhibitory effects on tumour cell growth.
Conjugated linoleic acids (CLAs) have recently received considerable attention, based on their ability to act both as preventive and therapeutic nutritional agents in rodent and tumour model systems. Previous studies have demonstrated CLA to have a very potent effect in inhibiting breast cancer cell growth. There is very little data available to determine what effect CLA has in prostate cancer, but the team have shown that CLA resulted in a dose- and time-dependent reduction in growth of LNCaP cells (androgen-senstive). Furthermore, exposure of CLA to PC3 cells (androgen-independent) caused growth inhibition of 20-35% with 12.5m M. The mechanisms by which CLA exerts effects at the cellular level remain to be fully clarified. Since proteins are the predominant effector molecules in the cell, proteomic technology will be used to enable the analysis of the expressed genome in a single experiment. This methodology will offer a better measure of cellular response than RNA or DNA.
Aim
The aim is to identify proteins, using proteomic technology, modulated by CLA in human prostate cancer cell lines.
This project will greatly benefit from the particular expertise provided by the Aberdeen Proteome Facility, which has extensive experience of protein characterisation.
The measurable outcome of this project will be the differences observed between untreated and treated cell lines, as detected by proteomic analysis. This may include qualitative (gain or loss of protein spots) and/or quantitative (increase or decrease of protein expression) differences. It will enable the team to adopt a "global approach" and identify proteins modulated by therapeutic doses of CLA. The increased understanding of the mechanisms by which CLA exerts anti-tumour effects at the cellular level will have important implications for therapeutic and preventative strategies.
Approved by Prostate Research Campaign UK Medical and Scientific Advisory Panel, and the Principal Committee.