Purpose: Peroxisome proliferator-activated receptor gamma (PPARgamma) 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/beta-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 PPARgamma and beta-Catenin were investigated among patients with breast cancer.
Methods: Using immunohistochemistry, we performed a study on 70 patient-derived human breast tumors and compared the protein expression levels of PPARgamma, beta-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 PPARgamma and beta-Catenin were performed on breast cancer tissues and cell lines to evaluate their protein level and molecular interaction.
Results: We showed that PPARgamma 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 beta-Catenin expression (P = 0.023), whereas no correlation was seen between PPARgamma 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 PPARgamma significantly correlated with long-term survival. Molecular interaction could also be demonstrated between PPARgamma and beta-Catenin both in breast cancer cell lines and tissue samples.
Conclusions: On the basis of these results, we suggested that PPARgamma might serve as a future target for the development of novel treatments in breast cancer.