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- Title
Regulation of c-met expression by transcription repressor Daxx.
- Authors
Morozov, V. M.; Massoll, N. A.; Vladimirova, O. V.; Maul, G. G.; Ishov, A. M.
- Abstract
The protooncogene c-met encodes the tyrosine kinase receptor for the hepatocyte growth factor/scatter factor (HGF/SF). While overexpression of c-met is documented in many types of tumors, the mechanism of c-met regulation remains elusive. Here, we demonstrate Daxx as a repressor of c-met transcription. The expression of c-met is elevated in Daxx knockout mouse cells and is reversed by Daxx reconstitution. C-met promoter analysis of Daxx−/− cells reveled changes in chromatin acetylation, but not in DNA methylation. Daxx binds to the mouse c-met promoter and Daxx-binding region is sufficient for transcription repression, while HDAC2 is associated with c-met promoter mostly in Daxx+/+ cells, pointing to Daxx-dependent HDAC2 recruitment as a potential mechanism of c-met repression. HGF-induced cell mobility and invasion confirmed augmented activity of c-Met/HGF pathway in Daxx−/− cells. Finally, inverse correlation between Daxx and c-Met in cancer cell lines and in metastatic breast cancer specimens suggests potential function of Daxx as a c-met repressor during cancer progression.Oncogene (2008) 27, 2177–2186; doi:10.1038/sj.onc.1210865; published online 22 October 2007
- Subjects
GENETIC regulation; MET receptor; PROTO-oncogenes; GENE expression; PROTEIN-tyrosine kinases; LIVER cells; CANCER cells; LABORATORY mice
- Publication
Oncogene, 2008, Vol 27, Issue 15, p2177
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1210865