Linked Life Data

18372914

Source:http://linkedlifedata.com/resource/pubmed/id/18372914

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
32
pubmed:dateCreated
2008-7-24
pubmed:abstractText
Beta-catenin accumulation is often found in lung tumors, but only a few patients have mutations in beta-catenin gene. In addition, activated p53 downregulates beta-catenin. Therefore, we postulated that alteration of the degradation complex AXIN2 (axis inhibition protein 2) and betaTrCP (beta-transducin repeat-containing protein) and p53 regulation could result in beta-catenin protein accumulation in lung cancer. Using the immunohistochemical and sequencing analyses, we found that patients with beta-catenin accumulation without mutation were associated with patients with p53 overexpression and low AXIN2 expression (P=0.023 approximately 0.041). Alteration of AXIN2 was associated with poor survival in early stage patients (P=0.016). Low expression of AXIN2 and betaTrCP was significantly associated with promoter hypermethylation and histone deacetylation. Ectopic expression and knockdown of p53, AXIN2 and betaTrCP genes in A549 (p53 wild-type) and H1299 (p53 null) lung cancer cell lines showed cooperation between p53 and AXIN2/betaTrCP in the reduction of beta-catenin expression. Our clinical and cell model findings provide new evidence that epigenetic silencing of AXIN2/betaTrCP in the degradation complex and deregulation of p53-mediated control lead to wild-type beta-catenin nuclear accumulation in non-small cell lung cancer tumorigenesis. In addition, a high level of p53 downregulates the beta-catenin expression, but this effect is attenuated by non-functional AXIN2 or betaTrCP in lung cancer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
24
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4488-96
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:18372914-Active Transport, Cell Nucleus, pubmed-meshheading:18372914-Axin Protein, pubmed-meshheading:18372914-Azacitidine, pubmed-meshheading:18372914-Carcinoma, Non-Small-Cell Lung, pubmed-meshheading:18372914-Cell Line, Tumor, pubmed-meshheading:18372914-Cell Nucleus, pubmed-meshheading:18372914-Cytoskeletal Proteins, pubmed-meshheading:18372914-DNA Methylation, pubmed-meshheading:18372914-Epigenesis, Genetic, pubmed-meshheading:18372914-Gene Silencing, pubmed-meshheading:18372914-Humans, pubmed-meshheading:18372914-Hydroxamic Acids, pubmed-meshheading:18372914-Lung Neoplasms, pubmed-meshheading:18372914-Prognosis, pubmed-meshheading:18372914-Promoter Regions, Genetic, pubmed-meshheading:18372914-Tumor Suppressor Protein p53, pubmed-meshheading:18372914-beta Catenin, pubmed-meshheading:18372914-beta-Transducin Repeat-Containing Proteins
pubmed:year
2008
pubmed:articleTitle
Epigenetic silencing of AXIN2/betaTrCP and deregulation of p53-mediated control lead to wild-type beta-catenin nuclear accumulation in lung tumorigenesis.
pubmed:affiliation
Department of Pharmacology, National Cheng Kung University, Tainan, Taiwan, ROC.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't