The Role of Prostaglandins in the Growth of Breast Epithelial Cells.

Abstract : Dietary fatty acids have been implicated as risk factors in breast carcinogenesis and our work, as well as that of others, has shown that they are regulators of the growth of breast epithelial cells. This project studied how linoleic acid and its metabolites stimulate the growth of breast epithelial cells. We found that this fatty acid causes induction of cyclooxygenase-2 by increasing transcription, and that this, in turn, generates products that stimulate growth. Linoleic acid and the products exert these action by binding to a target receptor, PPAR, which serves as a transcription factor that binds to an element in the promoter of the COX-2 gene, a mechanism identified for the first time in this project. We also discovered that the level of expression of COX-2 is controlled by the efficiency of translation of the mRNA and have shown that several proteins specifically mediate the effect. In summary, this project has determined the mechanism by which fatty acids stimulate the proliferation of breast cells, a process that offers the potential for intervention either by dietary manipulation or by chemoprevention using inhibitors of COX-2.