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RUNX3 is a prognostic marker and potential therapeutic target in human breast cancer

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Abstract

Purpose

To evaluate the role of RUNX3 in breast cancer pathogenesis, we examined the RUNX3 expression in breast cancer tissues and analyzed the correlation between RUNX3 expression and clinicopathologic variables and patients survival.

Methods

We evaluated the RUNX3 expression by immunohistochemistry using a tissue microarray containing 256 specimens of breast cancer patients. We also studied the role of RUNX3 in cell migration and invasion by performing cell migration and invasion assay. Differential expression of metastasis-related genes after RUNX3 restoration was analyzed using the Human Tumor Metastasis PCR Array.

Results

The RUNX3 expression was significantly correlated with breast cancer histology grade (P = 0.000), and low RUNX3 expression strongly correlated with worse 5-year overall and disease-specific survival rates (P = 0.000 and P = 0.001, respectively). Furthermore, we found that RUNX3 restoration suppressed breast cancer metastasis by controlling cell migration and invasion capacity. Finally, gene expression profiles of RUNX3-549 and Ctrl-549 cells showed matrix metalloproteinase-2 (MMP-2) was the most significant gene among the 84 metastasis-related genes influenced by RUNX3 reintroduction.

Conclusions

Reduced RUNX3 expression is significantly correlated with breast cancer progression and predicts worse survival. RUNX3 regulates breast cancer cell migration and invasion through the MMP-2 pathway.

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Acknowledgments

Grant support: This project is supported by grants from the National Natural Science Foundation of China (No. 81201636), the Science and Technology Department of Jiangsu province (No. BK2012139), and China Postdoctoral Science Foundation (No. 2012M511323).

Conflict of interest

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou, 221002, Jiangsu, China

    Jin Bai, Hong-Mei Yong, Fei-Fei Chen, Wen-Bo Song & Jun-Nian Zheng

  2. The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China

    Chen Li, Hui Liu & Jun-Nian Zheng

  3. School of Pathology, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou, 221002, Jiangsu, China

    Chen Li & Hui Liu

  4. Department of Oncological Sciences, Mount Sinai School of Medicine, New York, NY, USA

    Jin Bai

  5. Department of Medical Oncology, Huai’an Hospital to Xuzhou Medical College, Huai’an, Jiangsu, China

    Hong-Mei Yong

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  1. Jin Bai
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  2. Hong-Mei Yong
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  3. Fei-Fei Chen
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  4. Wen-Bo Song
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  5. Chen Li
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  6. Hui Liu
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  7. Jun-Nian Zheng
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Corresponding authors

Correspondence to Hui Liu or Jun-Nian Zheng.

Additional information

Jin Bai, Hong-Mei Yong and Fei-Fei Chen contributed equally to this paper.

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Bai, J., Yong, HM., Chen, FF. et al. RUNX3 is a prognostic marker and potential therapeutic target in human breast cancer. J Cancer Res Clin Oncol 139, 1813–1823 (2013). https://doi.org/10.1007/s00432-013-1498-x

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  • DOI: https://doi.org/10.1007/s00432-013-1498-x

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