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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 11/2007

01-11-2007 | Thoracic Oncology

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

Authors: Hong-Tao Xu, MD, PhD, Qiang Wei, MD, PhD, Yang Liu, MD, PhD, Lian-He Yang, MD, Shun-Dong Dai, MD, PhD, Yang Han, MD, PhD, Juan-Han Yu, MD, Nan Liu, MD, En-Hua Wang, MD, PhD

Published in: Annals of Surgical Oncology | Issue 11/2007

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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.
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Metadata
Title
Overexpression of Axin Downregulates TCF-4 and Inhibits the Development of Lung Cancer
Authors
Hong-Tao Xu, MD, PhD
Qiang Wei, MD, PhD
Yang Liu, MD, PhD
Lian-He Yang, MD
Shun-Dong Dai, MD, PhD
Yang Han, MD, PhD
Juan-Han Yu, MD
Nan Liu, MD
En-Hua Wang, MD, PhD
Publication date
01-11-2007
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 11/2007
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-007-9555-9

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