Overexpression of Axin Downregulates TCF-4 and Inhibits the Development of Lung Cancer
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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.
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.
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.
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.
KeywordsAxin T cell factor 4 Lung cancer Proliferation Invasion
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.165 to E.-H. Wang).
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