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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-11-20
pubmed:abstractText
Disruption of the DNA mismatch repair (MMR) system has been found to play an important role in sporadic human cancers of several organs such as colorectum, stomach, endometrium, and pancreas. In cancers of the former three organs, disruption of the MMR system is mainly caused by hypermethylation of the hMLH1 gene. We investigated the expression of the hMLH1 and hMSH2 proteins immunohistochemically in pancreatic and endometrial cancers with high frequency microsatellite instability (MSI-H). Loss of expression of hMLH1 was found in none of seven pancreatic cancer, whereas eight (57%) of 14 endometrial cancer showed loss of expression of hMLH1. On the other hand, one (14%) of seven pancreatic cancers and two (14%) of 14 endometrial cancers showed loss of hMSH2 expression. We further analyzed the methylation status at the promoter region of the hMLH1 and hMSH2 genes and found hypermethylation of hMLH1 at the promoter region in the great majority of endometrial cancers with loss of expression. However, no pancreatic cancer showed hypermethylation. We then further analyzed 22 pancreatic cancer cell lines and obtained similar results. These results suggested that MSI-H in pancreatic cancer is probably caused by different mechanisms from those of other sporadic cancers with MSI-H.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1019-6439
pubmed:author
pubmed:issnType
Print
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
535-41
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10938395-Adaptor Proteins, Signal Transducing, pubmed-meshheading:10938395-Adenocarcinoma, pubmed-meshheading:10938395-Carcinoma, pubmed-meshheading:10938395-Carrier Proteins, pubmed-meshheading:10938395-DNA, Neoplasm, pubmed-meshheading:10938395-DNA Methylation, pubmed-meshheading:10938395-DNA-Binding Proteins, pubmed-meshheading:10938395-Endometrial Neoplasms, pubmed-meshheading:10938395-Female, pubmed-meshheading:10938395-Gene Expression Regulation, Neoplastic, pubmed-meshheading:10938395-Gene Silencing, pubmed-meshheading:10938395-Humans, pubmed-meshheading:10938395-Microsatellite Repeats, pubmed-meshheading:10938395-MutS Homolog 2 Protein, pubmed-meshheading:10938395-Neoplasm Proteins, pubmed-meshheading:10938395-Nuclear Proteins, pubmed-meshheading:10938395-Pancreatic Neoplasms, pubmed-meshheading:10938395-Promoter Regions, Genetic, pubmed-meshheading:10938395-Proto-Oncogene Proteins, pubmed-meshheading:10938395-Tumor Cells, Cultured
pubmed:year
2000
pubmed:articleTitle
Not hMSH2 but hMLH1 is frequently silenced by hypermethylation in endometrial cancer but rarely silenced in pancreatic cancer with microsatellite instability.
pubmed:affiliation
Department of Molecular Pathology, Tohoku University School of Medicine, Aoba-ku, Sendai, Japan.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't