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DNA methylation-associated inactivation of TGFbeta-related genes DRM/Gremlin, RUNX3, and HPP1 in human cancers.
- Source :
- British Journal of Cancer; 10/31/2005, Vol. 93 Issue 9, p1029-1037, 9p, 1 Diagram, 5 Charts, 2 Graphs
- Publication Year :
- 2005
-
Abstract
- The transforming growth factor beta (TGFbeta)-signalling pathway is deregulated in many cancers. We examined the role of gene silencing via aberrant methylation of DRM/Gremlin and HPP1, which inhibit TGFbeta signalling, and RUNX3, which facilitates TGFbeta-signalling, of all genes that are thought to be tumour suppressors, are aberrantly expressed, and are thus thought to have important role in human cancers. We examined DRM/Gremlin mRNA expression in 44 cell lines and the promoter methylation status of DRM/Gremlin, HPP1, and RUNX3 in 44 cell lines and 511 primary tumours. The loss of DRM/Gremlin mRNA expression in human cancer cell lines is associated with DNA methylation, and treatment with the methylation inhibitor-reactivated mRNA expression (n=13). Methylation percentages of the three genes ranged from 0-83% in adult tumours and 0-50% in paediatric tumours. Methylation of DRM/Gremlin was more frequent in lung tumours in smokers, and methylation of all three genes was inversely correlated with prognosis in patients with bladder or prostate cancer. Our results provide strong evidence that these TGFbeta-related genes are frequently deregulated through aberrant methylation in many human malignancies. [ABSTRACT FROM AUTHOR]
- Subjects :
- CANCER
TRANSFORMING growth factors
DNA
METHYLATION
CANCER cells
IMMUNOMODULATORS
PROTEIN metabolism
BIOCHEMISTRY
COMPARATIVE studies
GENES
GROWTH factors
PHENOMENOLOGY
RESEARCH methodology
MEDICAL cooperation
MEMBRANE proteins
PROTEINS
RESEARCH
TUMORS
EVALUATION research
DNA methylation
CANCER cell culture
Subjects
Details
- Language :
- English
- ISSN :
- 00070920
- Volume :
- 93
- Issue :
- 9
- Database :
- Complementary Index
- Journal :
- British Journal of Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 18650396
- Full Text :
- https://doi.org/10.1038/sj.bjc.6602837