It is notable that men within both dietary arms of the study had significant associated with tumour progression

Within already initiated cells, although the precise pathways by which this is mediated have not been fully resolved. To what extent a broccoli-rich diet may influence these processes requires further studies. However, we consider it likely that it is the net effect of Albaspidin-AA changes in several pathways, as opposed to just TGFb1, which may underlie the observed reduction in both cancer and myocardial infarction through broccoli/crucifer consumption. A previous study has demonstrated that isothiocyanates can inhibit EGF signalling, but without a mechanistic explanation. In the current study, we show that SF will bind to the EGF ligand, and this may underlie our results and those reported previously. Moreover, chemical modification of signaling proteins by ITCs may be complemented by modification of receptor proteins, as has previously been shown for the TRPA1 receptor. Perturbation of signalling pathways is additionally determined by GSTM1 genotype. The interaction between diet and GSTM1 on gene expression may partially explain the contradictory results from those case control studies which lack dietary assessment and which have or have not associated the GSTM1 null genotype with enhanced risk of prostate cancer. GSTM1 enzyme activity catalyses both the formation and the cleavage of SF �C glutathione conjugates. We suggest that following transport into the plasma from enterocytes, GSTM1 activity catalyses the cleavage of the SF-glutathione conjugate within the low glutathione environment of the plasma to determine the extent of free SF that is available for protein modification, as discussed above, and which is not excreted via mercapturic acid metabolism. Thus low Benzoylaconine levels of SF, as would be expected from normal dietary consumption of broccoli, may lead to subtle changes in cell signalling, which, over time, result in profound changes in gene expression. In this manner, consuming one portion of broccoli per week if one is GSTM1 positive, or more if one is GSTM1 null, may contribute to a reduction in cancer risk. In addition to the insight this study provides to the effect of broccoli consumption on gene expression, we consider that our study may have broader implications. First, we demonstrate that routine prostate needle biopsies can be used for global gene expression analyses in addition to histological assessment, and that it is possible to monitor changes in expression with time.

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