Linked Life Data

12386812

Source:http://linkedlifedata.com/resource/pubmed/id/12386812

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
49
pubmed:dateCreated
2002-10-18
pubmed:abstractText
Lung cancer is a heterogeneous disease categorized into multiple subtypes of cancers which likely arise from distinct patterns of genetic alterations and disruptions. Precedent exists for a role of beta-catenin, a downstream component of the Wnt signaling pathway that serves as a transcriptional co-activator with TCF/LEF, in several human cancers including colon carcinomas. In this study, we observed that beta-catenin was highly and uniformly expressed in a panel of NSCLC cell lines and primary lung tumors. By contrast, gamma-catenin was weakly expressed or absent in several NSCLC cell lines and immunohistochemical analysis of primary NSCLC tumors revealed negligible to weak gamma-catenin staining in approximately 30% of the specimens. Treatment of NSCLC cells expressing reduced gamma-catenin protein with 5-aza-2'-deoxycytidine (5aza2dc), a DNA methylation inhibitor, or trichostatin A (TSA), a histone deacetylase inhibitor, increased gamma-catenin protein content in NSCLC cells with low gamma-catenin expression. Significantly, the activity of a beta-catenin/TCF-dependent luciferase reporter was markedly elevated in the NSCLC cell lines that underexpressed gamma-catenin relative to those lines that highly expressed gamma-catenin. Moreover, transfection of these cells with a gamma-catenin expression plasmid reduced the elevated TCF activity by 85% and strongly inhibited cell growth on tissue culture plastic as well as anchorage-independent growth in soft agar. This study shows that gamma-catenin can function as an inhibitor of beta-catenin/TCF-dependent gene transcription and highlights gamma-catenin as a potentially novel tumor suppressor protein in a subset of human NSCLC cancers.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
24
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7497-506
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
gamma-Catenin expression is reduced or absent in a subset of human lung cancers and re-expression inhibits transformed cell growth.
pubmed:affiliation
Veterans Administration Medical Center, Denver, Colorado, CO 80220, USA. robert.winn@uchsc.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.