Peroxisome proliferator activated receptor-gamma (PPAR-gamma) mediates the action of gamma linolenic acid in breast cancer cells.
Gamma linolenic acid (GLA) is a polyunsaturated fatty acid, which induces cytotoxicity and regulates cell adhesion in cancer cells. The molecular mechanism of these actions is not clear. We have shown that GLA acts via peroxisome proliferator activated receptors (PPARs), by stimulating their phosphorylation and translocation to the nucleus. Removing PPAR gamma with antisense oligos abolished the effect of GLA on the expression of adhesion molecules 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 breast cancer cells.
Jiang
W G
WG
Metastasis Research Group, University Department of Surgery, University of Wales College of Medicine, Cardiff, UK. jiangw@cf.ac.uk
Redfern
A
A
Bryce
R P
RP
Mansel
R E
RE
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007163:Immunosorbent Techniques; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010766:Phosphorylation; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured; D017965:gamma-Linolenic Acid / Q000494:pharmacology*
D016376:Oligonucleotides, Antisense; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D017965:gamma-Linolenic Acid