Peroxisome proliferator activated receptor γ protein expression is asymmetrically distributed in primary lung tumor and metastatic to lung osteosarcoma samples and does not correlate with gene methylation

Abstract

Background: Peroxisome proliferator activated receptor-γ (PPAR-γ) is a ligand-dependent transcription factor that plays important roles in cellular proliferation and differentiation. It has been implicated as a tumor suppressor in many solid tumors including human prostate, breast, colon, and lung cancer. The objective of this study was to determine the tissue distribution of PPAR-γ in normal canine lung, canine lung cancer, and metastatic to lung cancer, as well as determine the role, if any, of DNA methylation in epigenetic control of gene expression. The protein was studied using immunohistochemistry (IHC) and DNA methylation was studied using combined bisulfite restriction analysis (COBRA), and methylation-specific PCR (MSP). Results: PPAR-γ is expressed in all large conducting airways, particularly in goblet cells and bronchial glands, in the canine lung. The protein is also expressed in interstitial macrophages. PPAR-γ is expressed in 33 % of canine non-small cell lung cancer (NSCLC) cases and 66 % of metastatic osteosarcoma (OSA) cases. There is a significant loss of 5' PPAR-γ methylation from normal lung to primary lung cancer and metastatic OSA (p = 0.0002), however altered PPAR-γ promoter methylation at the interrogated locus does not appear to be associated with changes in protein expression. Conclusions: PPAR-γ protein is expressed in normal canine lung tissue, canine primary lung cancer, and metastatic OSA. Confirmation of PPAR-γ protein expression in tumor-bearing dogs supports the investigation of PPAR-γ agonists in this subset of veterinary patients. These results are the first to describe epigenetic marks and protein localization of PPAR-γ among different lung pathologies in the dog.