Mecanismes de l'acció moduladora dels lípids de la dieta sobre el càncer de mama experimental: influència sobre la funció de gens implicats en proliferació/diferenciació cel·lular

Several studies, including those of the research group, have demonstrated the protective and the stimulating actions of dietary n-9 monounsaturated (olive oil) and n-6 polyunsaturated (corn oil) lipids, respectively, on the experimental mammary cancer. The aim of this project is to investigate the mechanisms of such modulating actions. Specifically, we will evaluate those mechanisms related to changes in the proliferation and differentiation status of the mammary tumours through the modulation of the gene function. We will use an in vivo mammary cancer model, chemically-induced in the rat. We will analyse first the function of genes involved in cell proliferation and differentiation (c-erb B1/ EGFR, c-erbB2/neu and c-Ha-ras 1 protooncogenes and ß-actin). On a second approach, we will study genes identified previously through screening using the cDNA microarrays technology as modulates by n-6 dietary lipids in the experimental mammary tumors: a-2u submaxillary gland gloubin., H19, VDUP1 and the expressed sequence tag Rn. 32385. The study of the gene function will comprise the analysis of the expression at mRNA and protein level, the protein activity and the activation of the MAPK-mediated intracellular signal pathway. We will also characterize, from a histopathological perspective, the degree of differentiation of the mammary tumors caused by the dietary lipids. Finally, following an applied approach, we will analyse in vitro the relationship between the established molecular and histopathological phenotype of the mammary tumours and the changes in the chemotherapy treatment response of the tumour mammary cells. The correlation of the results of the molecular, anatomopathological and treatment studies with those of the clinical ones, obtained in the previous phase of the molecular, anatomopathological and treatment studies with those of the clinical ones, obtained in the previous phase of the study, will allow us to establish the biological profile conferr