Expression of peroxisome-proliferator activated receptor-gamma (PPARγ) and the PPAR-γ co-activator, PGC-I, in human breast cancer correlates with clinical outcomes

Peroxisome-proliferator activated receptor-gamma (PPARgamma) belongs to a family of nuclear receptors and acts as receptor for peroxisome-proliferators, steroids, retinoic acids, and polyunsaturated fatty acids. Our study examined the transcript levels of peroxisome-proliferator activated receptorgamma (PPARgamma) and its co-activator (PGC-I) in a cohort of patients with breast cancer. An invasive breast cancer cell, MDA MB 231 exhibited lower level of expression of PPAR-gamma compared to non-invasive MCF-7. Breast cancer tissues (n = 120) exhibited a lower level of PPAR-gamma mRNA compared to normal tissues (n = 25, p = 0.05). No difference, however, was seen with PGC-I. Although the levels of PPARgamma and PGC-I did not correlate with nodal involvement and grade, significantly lower levels of PPAR-gamma were seen in TNM3 and TNM4 tumors and from patients with local recurrence and those who died of breast cancer. Lowest level of PGC-I was also seen in TNM3 and TNM4 tumors and patients who died of breast cancer. We conclude that there is aberrant expression of PPARgamma and its co-activator, PGC-I, in human breast cancer and low levels of these molecules in cancer tissues are associated with poor clinical outcomes. (C) 2003 Wiley-Liss, Inc.