Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.1.1.37 (
DNA methyltransferase
)
4,983
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The receptor tyrosine kinase
EPHB2
has recently been shown to be a direct transcriptional target of TCF/beta-catenin. Premalignant lesions of the colon express high levels of
EPHB2
but the expression of this kinase is reduced or lost in most colorectal carcinomas. In addition, inactivation of
EPHB2
has been shown to accelerate tumorigenesis initiated by APC mutation in the colon and rectum. In this study, we investigated the molecular mechanisms responsible for the inactivation of
EPHB2
in colorectal tumors. We show here the presence of mutations in repetitive sequences in exon 17 of
EPHB2
in 6 of 29 adenomas with microsatellite instability (MSI), and 101 of 246 MSI carcinomas (21% and 41%, respectively). Moreover, we found
EPHB2
promoter hypermethylation in 54 of the 101 colorectal tumors studied (53%). Importantly,
EPHB2
expression was restored after treatment of
EPHB2
-methylated colon cancer cells with the
DNA methyltransferase
inhibitor 5-aza-2'-deoxycytidine. In conclusion, in this study, we elucidate the molecular mechanisms of inactivation of
EPHB2
and show for the first time the high incidence of frameshift mutations in MSI colorectal tumors and aberrant methylation of the regulatory sequences of this important tumor suppressor gene.
...
PMID:Mechanisms of inactivation of the receptor tyrosine kinase EPHB2 in colorectal tumors. 1628 1
