Linked Life Data

16297713

Source:http://linkedlifedata.com/resource/pubmed/id/16297713

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-11-21
pubmed:abstractText
Esophageal squamous cell carcinoma (ESCC) is one of the most common tumors in human. Previous studies showed that multiple genetic and epigenetic alterations involved in carcinogenesis of esophagus, whereas the molecular mechanisms are poorly understood. So far, more and more ESCC-related genes have been found and retinoic acid receptor beta(2) (RARbeta(2)) is such a gene which was recognized as a putative tumor suppressor gene since reduced RARbeta(2) mRNA expression has been observed in several solid tumors, including ESCC. A growing evidence indicated that RARbeta(2) was required for the growth inhibitory effect of retinoic acid (RA). However, the molecular mechanism of its inactivation remained obscure in ESCC. The RARbeta2 methylation status was assessed by methylation-specific PCR (MSP) in 12 ESCC cell lines and compared with their mRNA and protein expression level. Bisulfite sequencing of RARbeta(2) promoter region was performed to confirm the MSP results. After 5-aza-2'-deoxycytidine (5-aza-dc) treatment the expression of RARbeta(2) was reversed in two RARbeta(2)-downregulated cell lines. Therefore, hypermethylation of the promoter regions of RARbeta2 gene is a major mechanism of transcriptional inactivation and might be involved in tumor development of esophagus in some ESCC cell lines suggesting that multiple mechanisms contribute to the loss of RARbeta(2) expression in ESCC cell lines. Furthermore, the methylation status of RARbeta(2) promoter region and its expression was analyzed in 51 ESCC tissue samples with their adjacent normal epithelia and two normal esophageal epithelia. The results showed that there was a statistically significant correlation between methylation status of RARbeta(2) and tumor grade; Moreover, a relationship between methylation status and decreased RARbeta(2) expression was found only in G(2) stage tumors. After 5-aza-dc treatment, RARbeta(2) restoration was accompanied by growth inhibition and this might be one of the mechanisms but not the only mechanism for the tumor cell growth inhibition by 5-aza-dc. This study may have clinical applications for ESCC therapy and prevention.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0304-3835
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
230
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
271-83
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16297713-Adult, pubmed-meshheading:16297713-Aged, pubmed-meshheading:16297713-Aged, 80 and over, pubmed-meshheading:16297713-Antimetabolites, Antineoplastic, pubmed-meshheading:16297713-Azacitidine, pubmed-meshheading:16297713-Carcinoma, Squamous Cell, pubmed-meshheading:16297713-Cell Line, Tumor, pubmed-meshheading:16297713-Cell Proliferation, pubmed-meshheading:16297713-Cell Survival, pubmed-meshheading:16297713-DNA Methylation, pubmed-meshheading:16297713-DNA Modification Methylases, pubmed-meshheading:16297713-Esophageal Neoplasms, pubmed-meshheading:16297713-Esophagus, pubmed-meshheading:16297713-Female, pubmed-meshheading:16297713-Gene Expression Regulation, Neoplastic, pubmed-meshheading:16297713-Humans, pubmed-meshheading:16297713-Male, pubmed-meshheading:16297713-Middle Aged, pubmed-meshheading:16297713-RNA, Messenger, pubmed-meshheading:16297713-Receptors, Retinoic Acid
pubmed:year
2005
pubmed:articleTitle
5-Aza-2'-deoxycytidine induces retinoic acid receptor-beta(2) demethylation and growth inhibition in esophageal squamous carcinoma cells.
pubmed:affiliation
National Laboratory of Molecular Oncology, Cancer Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, Peoples Republic of China. liuzh@pubem.cicams.ac.cn
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't