Peroxisome proliferator activated receptor-gamma (PPAR-y) mediates the action of gamma linolenic acid in breast cancer cells

Gamma linolenic acid (GLA) is a polyunsaturated fatty acid, which induces c ytotoxicity and regulates cell adhesion in cancer cells. The molecular mech anism of these actions is not clear. We have shown that GLA acts via peroxi some proliferator activated receptors (PPARs), by stimulating their phospho rylation and translocation to the nucleus. Removing PPAR gamma with antisen se oligos abolished the effect of GLA on the expression of adhesion molecul es and tumour suppressor genes, whereas removal of PPAR alpha had no effect . Tissues from patients with breast cancer showed a reduction of expression of both PPARs in cancer tissues, as compared with normal. Thus, PPAR gamma serves as the receptor for GLA in the regulation of gene expression in bre ast cancer cells. (C) 2000 Harcourt Publishers Ltd.