Antitumoral effects of rosiglitazone are independent of PPAR gamma in NMU-induced tumors

NÚÑEZ M, GUTIÉRREZ A, COCCA C, MEDINA V, CROCI M, RIVERA E, MARTÍN G, BERGOC R

San Miguel de Tucuman, Argentina

Congreso; XLV Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2009

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

The thiazolidinediones such as Rosiglitazone (R) are antidiabetic agents acting through the activation of peroxisome proliferatoractivated receptor gamma (PPARg). PPARg ligands have recently been identified as potential targets for the treatment of human cancers including breast cancer. We have previously reported that R inhibits the tumor growth rate of mammary tumors induced in rats through the ip administration of N-Nitroso-N-methylurea (NMU). The aim of the present work was to investigate the expression of PPARg and proliferation markers in mammary normal tissue and NMU-induced tumors of untreated and R-treated (0.06 mg/Kg/day) rats. The percentage expression of PPARg and proliferating cell n u c l e a r a n t i g e n ( P C N A ) w a s d e t e rmi n e d b y immunohistochemistry. The PPARg expression was scarce in mammary tumors while it was significantly higher in normal mammary tissue (p<0.001). PPARg immunoreactivity was observed preferentially in the nucleus of ductal epithelial cells. On the other hand, PCNA expression was low in normal mammary tissue while it was higher in mammary tumors (p<0.001). In addition, R treatment significantly reduced PCNA (p<0.0001) while did not modify PPARg tumor expression. On the basis of the present results, we conclude that PPARg expression decreases during carcinogenesis and that the R antitumoral effects are independent of PPARg in this experimental model.