Promoter CpG methylation in cancer cells contributes to the regulation of MUC4
Open Access
- 6 January 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in British Journal of Cancer
- Vol. 100 (2), 344-351
- https://doi.org/10.1038/sj.bjc.6604845
Abstract
Mucin 4 (MUC4) is a high molecular weight transmembrane mucin that is overexpressed in many carcinomas and is a risk factor associated with a poor prognosis. In this study, we show that the DNA methylation pattern is intimately correlated with MUC4 expression in breast, lung, pancreas and colon cancer cell lines. We mapped the DNA methylation status of 94 CpG sites from −3622 to +29 using MassARRAY analysis that utilises base-specific cleavage of nucleic acids. MUC4-negative cancer cell lines and those with low MUC4 expression (eg, A427) were highly methylated near the transcriptional start site, whereas MUC4-positive cell lines (eg, NCI-H292) had low methylation levels. Moreover, 5-aza-2′-deoxycytidine and trichostatin A treatment of MUC4-negative cells or those with low MUC4 expression caused elevation of MUC4 mRNA. Our results suggest that DNA methylation in the 5′ flanking region play an important role in MUC4 gene expression in carcinomas of various organs. An understanding of epigenetic changes in MUC4 may contribute to the diagnosis of carcinogenic risk and prediction of outcome in patients with cancer.Keywords
This publication has 24 references indexed in Scilit:
- Transcriptional Gene Silencing Promotes DNA Hypermethylation through a Sequential Change in Chromatin Modifications in Cancer CellsCancer Research, 2004
- MUC4 is a novel prognostic factor of intrahepatic cholangiocarcinoma-mass forming typeHepatology, 2004
- Critical Role of Histone Methylation in Tumor Suppressor Gene Silencing in Colorectal CancerMolecular and Cellular Biology, 2003
- Muc4/sialomucin complex, the intramembrane ErbB2 ligand, induces specific phosphorylation of ErbB2 and enhances expression of p27kip, but does not activate mitogen-activated kinase or protein kinaseB/Akt pathwaysOncogene, 2002
- Isolation and characterization of MUC15, a novel cell membrane‐associated mucinEuropean Journal of Biochemistry, 2002
- MUC17, a Novel Membrane-Tethered MucinBiochemical and Biophysical Research Communications, 2002
- Ovarian cancer antigen CA125 is encoded by the MUC16 mucin geneInternational Journal of Cancer, 2002
- Characterization of Human Mucin Gene MUC4PromoterJournal of Biological Chemistry, 2001
- The essentials of DNA methylationCell, 1992
- Similarity of protein encoded by the human c-erb-B-2 gene to epidermal growth factor receptorNature, 1986