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PPARγ and Wnt/β-Catenin pathway in human breast cancer: expression pattern, molecular interaction and clinical/prognostic correlations

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

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Abbreviations

PPARγ:

Peroxisome proliferator-activated receptor γ

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Acknowledgments

This work was supported by Specialized Research Fund for the Doctoral Program of Higher Education (for new teachers, No. 20070246131), Natural Scientific Foundation of Jiangsu Province Grant (No. BK2006546 and No. BK2006547), Jiangsu “six personnel peak” talent-funded projects (No. 2006113), Doctoral start-up research fund of Nantong University(No. 03080174), the National Natural Scientific Foundation of China Grant (No. 30872320 and No. 30770488), and College and University Natural Scientific Research Program of Jiangsu Province (No. 03KJB180109, No. 04KJB320114 and No. 07KJD310172), Technology Guidance Plan for Social Development of Jiangsu Province Grant (BS2004526).

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Authors and Affiliations

  1. Department of General Surgery, Zhongshan Hospital, Fudan University, 200032, Shanghai, China

    Ying Jiang, Weiqi Lu, Yong Zhang & Hua Zhang

  2. Breast Disease Center, Affiliated Hospital of Nantong University, 226001, Jiangsu, China

    Ying Jiang, Chunhui Zhang & Junfei Xu

  3. Department of Pathology, Affiliated Cancer Hospital of Nantong University, Medical College of Nantong University, 226001, Nantong, China

    Lin Zou, Song He, Chun Cheng & Donglin Wang

  4. The Jiangsu Province Key Lab of Neuroregeneration, Nantong University, 226001, Nantong, People’s Republic China

    Aiguo Shen

Authors
  1. Ying Jiang
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  2. Lin Zou
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  3. Chunhui Zhang
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  4. Song He
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  9. Hua Zhang
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  10. Donglin Wang
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Corresponding authors

Correspondence to Ying Jiang, Donglin Wang or Aiguo Shen.

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Y. Jiang and L. Zou contributed equally to this work.

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Jiang, Y., Zou, L., Zhang, C. et al. PPARγ and Wnt/β-Catenin pathway in human breast cancer: expression pattern, molecular interaction and clinical/prognostic correlations. J Cancer Res Clin Oncol 135, 1551–1559 (2009). https://doi.org/10.1007/s00432-009-0602-8

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  • DOI: https://doi.org/10.1007/s00432-009-0602-8

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