The localisation and reduction of nuclear staining of PPARgamma and PGC-1 in human breast cancer.

Peroxisome proliferator activated receptor-gamma (PPARgamma) belongs to a family of nuclear receptors and acts as a receptor for peroxisome proliferators, steroids, retinoic acids and polyunsaturated fatty acids. The current study examined both the transcript levels of PPARgamma and its coactivator PGC-1, and the localisation of these molecules in breast cancer tissues. Both PPARgamma and PGC-1 were located exclusively within the nucleus of epithelium and breast cancer tissues. Nuclear staining of both molecules was weaker in cancer cells compared with normal mammary epithelium. Computerised image analysis was used to quantify the immunohistochemical staining intensity, and this demonstrated that normal back-ground breast tissue exhibited higher levels of both PPARgamma (mean +/- sd, 4.57+/-1.03) and PGC-1 (2.84+/-0.64), respectively. In contrast, tumour tissue exhibited significantly lower levels of PPARgamma (1.45+/-0.74, p<0.001 versus normal background tissue) and for PGC-1 (1.23+/-0.60, p<0.001 versus normal background tissue). This study also showed a variation in the levels of PGC-1 and PPARgamma between ductal and lobular tumours. These findings were corroborated by mRNA analysis which also demonstrated lower levels of both PGC-1 and PPARgamma in breast tumour tissue. It is concluded that both PPARgamma and its coactivator PGC-1 play important roles in the development and progression of breast cancer, and may have a significant bearing on patient prognosis.