Expression of peroxisome-proliferator activated receptor-gamma (PPARgamma) and the PPARgamma co-activator, PGC-1, 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 receptor-gamma (PPARgamma) and its co-activator (PGC-1) in a cohort of patients with breast cancer. An invasive breast cancer cell, MDA MB 231 exhibited lower level of expression of PPARgamma, compared to non-invasive MCF-7. Breast cancer tissues (n = 120) exhibited a lower level of PPARgamma mRNA compared to normal tissues (n = 25, p = 0.05). No difference, however, was seen with PGC-1. Although the levels of PPARgamma and PGC-1 did not correlate with nodal involvement and grade, significantly lower levels of PPARgamma were seen in TNM3 and TNM4 tumors and from patients with local recurrence and those who died of breast cancer. Lowest level of PGC-1 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-1, in human breast cancer and low levels of these molecules in cancer tissues are associated with poor clinical outcomes. Copyright 2003 Wiley-Liss, Inc.