The Epstein–Barr virus oncogene product, latent membrane protein 1, induces the downregulation of E-cadherin gene expression via activation of DNA methyltransferases

作者: C.-N. Tsai , C.-L. Tsai , K.-P. Tse , H.-Y. Chang , Y.-S. Chang

DOI: 10.1073/PNAS.152059399

关键词:

摘要: The latent membrane protein (LMP1) of Epstein–Barr virus (EBV) is expressed in EBV-associated nasopharyngeal carcinoma, which notoriously metastatic. Although it established that LMP1 represses E-cadherin expression and enhances the invasive ability carcinoma cells, mechanism underlying this repression remains to be elucidated. In study, we demonstrate induces activity DNA methyltransferases 1, 3a, 3b, using real-time reverse transcription–PCR enzyme assay. This results hypermethylation promoter down-regulation gene expression, as revealed by methylation-specific PCR, Western blotting data. methyltransferase inhibitor, 5′-Aza-2′dC, restores LMP1-expressing turn blocks cell migration ability, demonstrated Transwell Our findings suggest down-regulates cellular methylation machinery.

参考文章(40)
Kwang-Rok Kim, Tomokazu Yoshizaki, Hisashi Miyamori, Kazuki Hasegawa, Toshiyuki Horikawa, Mitsuru Furukawa, Shizuko Harada, Motoharu Seiki, Hiroshi Sato, Transformation of Madin-Darby canine kidney (MDCK) epithelial cells by Epstein-Barr virus latent membrane protein 1 (LMP1) induces expression of Ets1 and invasive growth Oncogene. ,vol. 19, pp. 1764- 1771 ,(2000) , 10.1038/SJ.ONC.1203502
Anne-Karina Perl, Petra Wilgenbus, Ulf Dahl, Henrik Semb, Gerhard Christofori, A causal role for E-cadherin in the transition from adenoma to carcinoma Nature. ,vol. 392, pp. 190- 193 ,(1998) , 10.1038/32433
Ina Rhee, Kam-Wing Jair, Ray-Whay Chiu Yen, Christoph Lengauer, James G. Herman, Kenneth W. Kinzler, Bert Vogelstein, Stephen B. Baylin, Kornel E. Schuebel, CpG methylation is maintained in human cancer cells lacking DNMT1 Nature. ,vol. 404, pp. 1003- 1007 ,(2000) , 10.1038/35010000
K.-W. Lo, D. P. Huang, K.-F. Mak, J. K. S. Woo, Y.-S. Tsang, A. Van Hasselt, S.-F. Leung, J. C. K. Lee, Y.-F. Chung, S.-T. Cheung, Hypermethylation of the p16 Gene in Nasopharyngeal Carcinoma Cancer Research. ,vol. 56, pp. 2721- 2725 ,(1996)
Kwok-Wai Lo, Joseph Kwong, Angela Bik-Yu Hui, Sylvia Yat-Yee Chan, Ka-Fai To, Andrew Siu-Chung Chan, Lillian Shuk-Nga Chow, Peter ML Teo, Philip J Johnson, Dolly Poon Huang, None, High Frequency of Promoter Hypermethylation of RASSF1A in Nasopharyngeal Carcinoma Cancer Research. ,vol. 61, pp. 3877- 3881 ,(2001)
L. M. Weiss, D. Shibata, Epstein-Barr virus-associated gastric adenocarcinoma. American Journal of Pathology. ,vol. 140, pp. 769- 774 ,(1992)
P Lou, W Chen, T Sheen, J Ko, M Hsu, J Wu, Expression of E-cadherin/catenin complex in nasopharyngeal carcinoma: correlation with clinicopathological parameters. Oncology Reports. ,vol. 6, pp. 1065- 1136 ,(1999) , 10.3892/OR.6.5.1065
Shuko Nakayama, Akira Sasaki, Hiroshi Mese, Rafael E. Alcalde, Takanori Tsuji, Tomohiro Matsumura, The E-cadherin gene is silenced by CpG methylation in human oral squamous cell carcinomas International Journal of Cancer. ,vol. 93, pp. 667- 673 ,(2001) , 10.1002/IJC.1386