Annals of Surgical Oncology

, Volume 14, Issue 11, pp 3251–3259 | Cite as

Overexpression of Axin Downregulates TCF-4 and Inhibits the Development of Lung Cancer

  • Hong-Tao Xu
  • Qiang Wei
  • Yang Liu
  • Lian-He Yang
  • Shun-Dong Dai
  • Yang Han
  • Juan-Han Yu
  • Nan Liu
  • En-Hua Wang
Thoracic Oncology Original Papers

Abstract

Background

T cell factor 4 (TCF-4) mediates a nuclear response to wingless/int (Wnt) signals by interacting with β-catenin. Axis inhibition protein (axin) is an important negative regulator of the Wnt signaling pathway. Our aims were to examine the relationship between axin and TCF-4 and to explore the effects of axin on the development of lung cancer.

Methods

Expression levels of axin and TCF-4 were examined in 107 lung cancer specimens by immunohistochemistry. The axin gene was transfected into lung cancer BE1 cells. The expression levels of axin, β-catenin, and TCF-4 were detected with immunofluorescence and reverse transcription-polymerase chain reaction (RT-PCR) experiments. Apoptosis, proliferation, and the invasive ability of lung cancer cells were examined using flow cytometry, 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT), and Matrigel invasive assays.

Results

Preserved axin expression correlated negatively with TCF-4 expression (P = .031). Axin expression differed with respect to degree of differentiation (P = .025) and histological tumor type (P = .031). TCF-4 expression differed relative to tumor, node metastasis (TNM) stage (P = .024). BE1 cells transfected with axin (BE1-axin cells) exhibited a significant decrease in TCF-4 expression. The level of apoptosis in BE1-axin cells was significantly increased, while the proliferative and invasive abilities of BE1-axin cells were decreased.

Conclusion

These results suggest that reduced expression of axin or augmented expression of TCF-4 is associated with the malignant behavior of lung cancers. Overexpression of axin can downregulate expression of TCF-4 and can inhibit the ability of lung cancer cells to proliferate and invade.

Keywords

Axin T cell factor 4 Lung cancer Proliferation Invasion 

Notes

ACKNOWLEDGMENTS

We thank Dr. Jie Zheng at Medical College of Beijing University, China for providing lung cancer BE1 cell lines. We also thank Professor Mark A. Perrella at Brigham & Women’s Hospital, Boston, MA, USA for kindly providing axin expression vector pFLAG-CMV-5b-axin containing mouse axin1 gene.

This study was supported by National Natural Science Foundation of China (Grants 30470764 and 30670917 to E.-H. Wang) and Doctoral Fund of Ministry of Education of China (No.[2004]165 to E.-H. Wang).

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Copyright information

© Society of Surgical Oncology 2007

Authors and Affiliations

  • Hong-Tao Xu
    • 1
  • Qiang Wei
    • 1
  • Yang Liu
    • 1
  • Lian-He Yang
    • 1
  • Shun-Dong Dai
    • 1
  • Yang Han
    • 1
  • Juan-Han Yu
    • 1
  • Nan Liu
    • 1
  • En-Hua Wang
    • 1
  1. 1.Department of Pathology, College of Basic Medical SciencesChina Medical University and Department of Pathology, the First Affiliated Hospital of China Medical UniversityShenyangChina

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