PMID- 17952115
OWN - NLM
STAT- MEDLINE
DCOM- 20080429
LR  - 20201209
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 27
IP  - 15
DP  - 2008 Apr 3
TI  - Regulation of c-met expression by transcription repressor Daxx.
PG  - 2177-86
AB  - 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.
FAU - Morozov, V M
AU  - Morozov VM
AD  - Department of Anatomy & Cell Biology and Shands Cancer Center, University of 
      Florida, Gainesville, FL, USA.
FAU - Massoll, N A
AU  - Massoll NA
FAU - Vladimirova, O V
AU  - Vladimirova OV
FAU - Maul, G G
AU  - Maul GG
FAU - Ishov, A M
AU  - Ishov AM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071022
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Carrier Proteins)
RN  - 0 (Chromatin)
RN  - 0 (Co-Repressor Proteins)
RN  - 0 (Daxx protein, mouse)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Molecular Chaperones)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Repressor Proteins)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 3.5.1.98 (Hdac2 protein, mouse)
RN  - EC 3.5.1.98 (Histone Deacetylase 2)
RN  - EC 3.5.1.98 (Histone Deacetylases)
SB  - IM
MH  - Animals
MH  - Breast Neoplasms/genetics/metabolism
MH  - Carcinoma/genetics/metabolism
MH  - Carrier Proteins/genetics/metabolism/*physiology
MH  - Cell Movement/genetics
MH  - Chromatin/metabolism
MH  - Co-Repressor Proteins
MH  - DNA Methylation
MH  - Disease Progression
MH  - Down-Regulation
MH  - *Gene Expression Regulation
MH  - Histone Deacetylase 2
MH  - Histone Deacetylases/metabolism
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/genetics/metabolism/*physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Molecular Chaperones
MH  - Nuclear Proteins/genetics/metabolism/*physiology
MH  - Promoter Regions, Genetic
MH  - Protein Binding
MH  - Proto-Oncogene Proteins c-met/*genetics
MH  - Repressor Proteins/genetics/metabolism/physiology
MH  - Sequence Deletion
MH  - Tumor Cells, Cultured
MH  - Wound Healing/genetics
EDAT- 2007/10/24 09:00
MHDA- 2008/04/30 09:00
CRDT- 2007/10/24 09:00
PHST- 2007/10/24 09:00 [pubmed]
PHST- 2008/04/30 09:00 [medline]
PHST- 2007/10/24 09:00 [entrez]
AID - 1210865 [pii]
AID - 10.1038/sj.onc.1210865 [doi]
PST - ppublish
SO  - Oncogene. 2008 Apr 3;27(15):2177-86. doi: 10.1038/sj.onc.1210865. Epub 2007 Oct 
      22.