Prognostic and biological significance of peroxisome proliferator-activated receptor-gamma in luminal breast cancer
Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor expressed in a large number of human cancers and plays important roles in breast cancer cell proliferation. Its association with clinicopathologic features and Wnt/β-Catenin signaling pathway, a crucial factor in embryonic and malignant development, in breast cancer has not been reported systematically. In the present study, expression patterns, interaction and the correlations with clinical/prognostic factors of PPARγ and β-Catenin were investigated among patients with breast cancer. Using immunohistochemistry, we performed a study on 70 patient-derived human breast tumors and compared the protein expression levels of PPARγ, β-Catenin and Ki-67. Correlations were then analyzed between IHC-assessed level of these molecules and major clinicopathologic variables and survival. Furthermore, western blot (WB) analysis before and after immunoprecipitation with PPARγ and β-Catenin were performed on breast cancer tissues and cell lines to evaluate their protein level and molecular interaction. We showed that PPARγ expression was of significant prognostic value in the outcome of breast carcinomas, which positively correlated with ER status (P = 0.012) and inversely associated with histologic grade (P = 0.012), tumor size (P = 0.007), axillary lymph node status (P = 0.044), TNM stage (P = 0.026), Ki-67 (P = 0.006) and abnormal β-Catenin expression (P = 0.023), whereas no correlation was seen between PPARγ and age (P = 0.513), histology (P = 0.764), PR (P = 0.099) or HER-2 status (P = 0.175). Kaplan–Meier survival curves of the study population showed that high expression level of PPARγ significantly correlated with long-term survival. Molecular interaction could also be demonstrated between PPARγ and β-Catenin both in breast cancer cell lines and tissue samples. On the basis of these results, we suggested that PPARγ might serve as a future target for the development of novel treatments in breast cancer.