Author:
Yang Lian-He,Xu Hong-Tao,Han Yang,Li Qing-Chang,Liu Yang,Zhao Yue,Yang Zhi-Qiang,Dong Qian-Ze,Miao Yuan,Dai Shun-Dong,Wang En-Hua
Abstract
Abstract
Background
We previously reported that overexpression of Axin downregulates T cell factor-4 (TCF-4) transcription. However, the mechanism(s) by which Axin downregulates the transcription and expression of TCF-4 is not clear. It has been reported that β-catenin promotes and p53 inhibits TCF-4 transcription, respectively. The aim of this study was to investigate whether β-catenin and/or p53 is required for Axin-mediated downregulation of TCF-4.
Results
Axin mutants that lack p53/HIPK2 and/or β-catenin binding domains were expressed in lung cancer cells, BE1 (mutant p53) and A549 (wild type p53). Expression of Axin or AxinΔp53 downregulates β-catenin and TCF-4, and knock-down of β-catenin upregulates TCF-4 in BE1 cells. However, expression of AxinΔβ-ca into BE1 cells did not downregulate TCF-4 expression. These results indicate that Axin downregulates TCF-4 transcription via β-catenin. Although overexpression of wild-type p53 also downregulates TCF-4 in BE1 cells, cotransfection of p53 and AxinΔβ-ca did not downregulate TCF-4 further. These results suggest that Axin does not promote p53-mediated downregulation of TCF-4. Axin, AxinΔp53, and AxinΔβ-ca all downregulated β-catenin and TCF-4 in A549 cells. Knock-down of p53 upregulated β-catenin and TCF-4, but cotransfection of AxinΔβ-ca and p53 siRNA resulted in downregulation of β-catenin and TCF-4. These results indicate that p53 is not required for Axin-mediated downregulation of TCF-4. Knock-down or inhibition of GSK-3β prevented Axin-mediated downregulation of TCF-4. Furthermore, expression of Axin and AxinΔp53, prevented the proliferative and invasive ability of BE1 and A549, expression of AxinΔβ-ca could only prevented the proliferative and invasive ability effectively.
Conclusions
Axin downregulates TCF-4 transcription via β-catenin and independently of p53. Axin may also inhibits the proliferation and invasion of lung cancer cells via β-catenin and p53.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology,Molecular Medicine
Reference34 articles.
1. Lustig B, Behrens J: The Wnt signaling pathway and its role in tumor development. J Cancer Res Clin Oncol. 2003, 129: 199-221.
2. Ueta T, Ikeguchi M, Hirooka Y, Kaibara N, Terada T: Beta-catenin and cyclin D1 expression in human hepatocellular carcinoma. Oncol Rep. 2002, 9: 1197-1203.
3. Gerstein AV, Almeida TA, Zhao G, Chess E, Shih IeM, Buhler K, Pienta K, Rubin MA, Vessella R, Papadopoulos N: APC/CTNNB1 (beta-catenin) pathway alterations in human prostate cancers. Genes Chromosomes Cancer. 2002, 34: 9-16. 10.1002/gcc.10037
4. Cheng XX, Sun Y, Chen XY, Zhang KL, Kong QY, Liu J, Li H: Frequent translocalization of beta-catenin in gastric cancers and its relevance to tumor progression. Oncol Rep. 2004, 11: 1201-1207.
5. Xu HT, Wang L, Lin D, Liu Y, Liu N, Yuan XM, Wang EH: Abnormal beta-catenin and reduced axin expression are associated with poor differentiation and progression in non-small cell lung cancer. Am J Clin Pathol. 2006, 125: 534-541.
Cited by
29 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献