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Peroxisome proliferator‐activated receptor gamma as a molecular target of polyunsaturated fatty acids in breast cancer cells
Author(s) -
Allred Clinton D,
Talbert Dominique R,
Kilgore Michael W
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a560-b
Subject(s) - peroxisome proliferator activated receptor , peroxisome , peroxisome proliferator activated receptor gamma , cancer research , transfection , reporter gene , peroxisome proliferator activated receptor delta , receptor , estrogen receptor , nuclear receptor , cancer cell , chemistry , microbiology and biotechnology , cell culture , biology , endocrinology , cancer , medicine , breast cancer , biochemistry , gene expression , transcription factor , gene , genetics
Studies have shown that individual sources of dietary fat influence breast cancer development and growth. Linoleic acid (LAA) induces proliferation and other physiological responses in estrogen‐dependent breast cancer (MCF‐7) cells. However, how LAA elicits these effects remains unclear. We hypothesize that peroxisome proliferator‐activated receptor gamma (PPARγ ), which is over expressed in MCF‐7 cells, serves as a molecular target of LAA. The purpose of these studies was to examine whether LAA functions directly through PPARγ and to determine if LAA is itself a ligand of PPARγ. Utilizing a PPARγ response element (PPRE)‐mediated reporter construct, we demonstrate that LAA activates the reporter in MCF‐7 cells and that this effect is inhibited by GW 9662, a known PPARγ antagonist. We then expressed the receptor in a prostate cancer cell line (22Rv1) that is PPARγ negative. When these cells were co‐transfected with a PPARγ expression plasmid, LAA induced the PPRE‐reporter. Also, LAA induced the PPRE‐reporter when co‐treated with salicylic acid, an inhibitor of cyclooxygenase activity, suggesting that the metabolism of LAA to prostaglandins is unnecessary. Downstream targets of PPARγ and physiological actions of LAA acting through the receptor have also been assessed. Therefore, it appears that LAA directly activates PPARγ which provides a potential molecular link to the physiological actions of this fatty acid in breast cancer. This work was supported by grants W81XWH‐04‐1‐0532 from the DOD to CDA, R01 CA95609‐01 from NIH to MWK, and 1F31CA117235‐01 from NIH to DRT.