Ppar Gamma And Wnt/Beta-Catenin Pathway In Human Breast Cancer: Expression Pattern, Molecular Interaction And Clinical/Prognostic Correlations

Peroxisome proliferator-activated receptor gamma (PPAR gamma) 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 PPAR gamma and beta-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 PPAR gamma, 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 PPAR gamma and beta-Catenin were performed on breast cancer tissues and cell lines to evaluate their protein level and molecular interaction.We showed that PPAR gamma 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 PPAR gamma 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 PPAR gamma significantly correlated with long-term survival. Molecular interaction could also be demonstrated between PPAR gamma and beta-Catenin both in breast cancer cell lines and tissue samples.On the basis of these results, we suggested that PPAR gamma might serve as a future target for the development of novel treatments in breast cancer.