Linked Life Data

18974146

Source:http://linkedlifedata.com/resource/pubmed/id/18974146

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
2008-10-31
pubmed:abstractText
A better understanding of key molecular changes during transformation of lung epithelial cells could affect strategies to reduce mortality from lung cancer. This study uses an in vitro model to identify key molecular changes that drive cell transformation and the likely clonal outgrowth of preneoplastic lung epithelial cells that occurs in the chronic smoker. Here, we show differences in transformation efficiency associated with DNA repair capacity for two hTERT/cyclin-dependent kinase 4, immortalized bronchial epithelial cell lines after low-dose treatment with the carcinogens methylnitrosourea, benzo(a)pyrene-diolepoxide 1, or both for 12 weeks. Levels of cytosine-DNA methyltransferase 1 (DNMT1) protein increased significantly during carcinogen exposure and were associated with the detection of promoter hypermethylation of 5 to 10 genes in each transformed cell line. Multiple members of the cadherin gene family were commonly methylated during transformation. Stable knockdown of DNMT1 reversed transformation and gene silencing. Moreover, stable knockdown of DNMT1 protein before carcinogen treatment prevented transformation and methylation of cadherin genes. These studies provide a mechanistic link between increased DNMT1 protein, de novo methylation of tumor suppressor genes, and reduced DNA repair capacity that together seem causal for transformation of lung epithelial cells. This finding supports the development of demethylation strategies for primary prevention of lung cancer in smokers.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1538-7445
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
68
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9005-14
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Carcinogen-induced gene promoter hypermethylation is mediated by DNMT1 and causal for transformation of immortalized bronchial epithelial cells.
pubmed:affiliation
Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural