Linked Life Data

18404674

Source:http://linkedlifedata.com/resource/pubmed/id/18404674

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-6-2
pubmed:abstractText
Epigenetic aberration is known to be important in human carcinogenesis. Promoter methylation status of RAS effector related genes, RASSF1A, RASSF2A, hDAB2IP (m2a and m2b regions) and BLU, was evaluated in 76 endometrial carcinomas and their non-neoplastic endometrial tissue by methylation specific PCR. Hypermethylation of at least one of the 5 genes was detected in 73.7% of carcinomas. There were significant correlations between methylation of hDAB2IP and RASSF1A, RASSF2A (p = 0.042, p = 0.012, respectively). Significantly, more frequent RASSF1A hypermethylation was found in Type I endometrioid carcinomas than Type II carcinomas (p = 0.049). Among endometrioid cancers, significant association between RASSF1A hypermethylation and advanced stage, as well as between methylation of hDAB2IP at m2a region with deep myometrial invasion (p < 0.05) was observed. mRNA expression of RASSF1A, RASSF2A and BLU in endometrial cancer cell lines significantly increased after treatment with the demethylating agent 5-Aza-2'-deoxycytidine supporting the repressive effect of hypermethylation on their transcription. Immunohistochemical study of DNMT1 on eight normal endometrium, 16 hyperplastic endometrium without atypia, 40 atypical complex hyperplasia and 79 endometrial carcinomas showed progressive increase in DNMT1 immunoreactivity from normal endometrium to endometrial hyperplasia and endometrioid carcinomas (p = 0.001). Among carcinomas, distinctly higher DNMT1 expression was observed in Type I endometrioid carcinomas (p < 0.001). DNMT1 immunoreactivity correlated with RASSF1A and RASSF2A methylation (p < 0.05). The data suggested that hypermethylation of RAS related genes, particularly RASSF1A, was involved in endometrial carcinogenesis with possible divergent patterns in different histological types. DNMT1 protein overexpression might contribute to such aberrant DNA hypermethylation of specific tumor suppressor genes in endometrial cancers.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1097-0215
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
123
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
296-302
pubmed:meshHeading
pubmed-meshheading:18404674-Adult, pubmed-meshheading:18404674-Aged, pubmed-meshheading:18404674-Aged, 80 and over, pubmed-meshheading:18404674-Carcinoma, Endometrioid, pubmed-meshheading:18404674-DNA Methylation, pubmed-meshheading:18404674-DNA Primers, pubmed-meshheading:18404674-Endometrial Neoplasms, pubmed-meshheading:18404674-Female, pubmed-meshheading:18404674-Gene Expression Regulation, Enzymologic, pubmed-meshheading:18404674-Gene Expression Regulation, Neoplastic, pubmed-meshheading:18404674-Genes, Tumor Suppressor, pubmed-meshheading:18404674-Genes, ras, pubmed-meshheading:18404674-Humans, pubmed-meshheading:18404674-Immunohistochemistry, pubmed-meshheading:18404674-Middle Aged, pubmed-meshheading:18404674-Polymerase Chain Reaction, pubmed-meshheading:18404674-Proteins, pubmed-meshheading:18404674-RNA, Messenger, pubmed-meshheading:18404674-Repressor Proteins, pubmed-meshheading:18404674-Tumor Suppressor Proteins, pubmed-meshheading:18404674-ras GTPase-Activating Proteins
pubmed:year
2008
pubmed:articleTitle
Hypermethylation of RAS effector related genes and DNA methyltransferase 1 expression in endometrial carcinogenesis.
pubmed:affiliation
Department of Pathology, the University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't