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)
To identify potentially important genes dysregulated in pancreatic cancer, we analyzed genome-wide transcriptional analysis of pancreatic cancers and normal pancreatic duct samples and identified the transcriptional coactivator,
EYA2
(Drosophila Eyes Absent Homologue-2) as silenced in the majority of pancreatic cancers. We investigated the role of epigenetic mechanisms of
EYA2
gene silencing in pancreatic cancers, performed in vitro and in vivo proliferation and migration assays to assess the effect of
EYA2
silencing on tumor cell growth and metastasis formation, and expression analysis to identify genes transcriptionally regulated by
EYA2
. We found loss of tumoral Eya2 expression in 63% of pancreatic cancers (120/189 cases). Silencing of
EYA2
expression in pancreatic cancer cell lines correlated with promoter methylation and histone deacetylation and was reversible with
DNA methyltransferase
and HDAC inhibitors.
EYA2
knockdown in pancreatic cancer cell lines increased cell proliferation. Compared to parental pancreatic cancer cells, pancreatic cancers stably-expressing
EYA2
grew more slowly and had fewer metastases in orthotopic models. The transcriptional changes after stable expression of
EYA2
in pancreatic cancer cells included induction of genes in the TGFbeta pathway. Epigenetic silencing of
EYA2
is a common event in pancreatic cancers and stable expression
EYA2
limits the growth and metastases of pancreatic adenocarcinoma.
...
PMID:Epigenetic silencing of EYA2 in pancreatic adenocarcinomas promotes tumor growth. 2481 Sep 6
