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J Cancer Res Clin Oncol. 2009 Nov;135(11):1551-9. doi: 10.1007/s00432-009-0602-8. Epub 2009 Jun 3.

PPARgamma and Wnt/beta-Catenin pathway in human breast cancer: expression pattern, molecular interaction and clinical/prognostic correlations.

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  • 1Department of General Surgery, Zhongshan Hospital, Fudan University, 200032 Shanghai, China. jiangy05@yahoo.com

Abstract

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.

PMID:
19495794
[PubMed - indexed for MEDLINE]
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