Linked Life Data

17483318

Source:http://linkedlifedata.com/resource/pubmed/id/17483318

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2007-5-7
pubmed:abstractText
Although several lines of evidence suggest the involvement of the Wnt pathway in the development of gastric cancers, the functional significance of the pathway in gastric carcinogenesis is still poorly defined. To examine the role of the Apc/beta-catenin signaling pathway in the development of gastric cancers, we investigated the gastric mucosa of the Apc(Min/+) mouse, which is a murine model for familial adenomatous polyposis, carrying a germ-line mutation at codon 850 of Apc. We found that aged Apc(Min/+) mice spontaneously develop multiple tumors in the stomach, which are accompanied by loss of heterozygosity of Apc. Such tumors consisted of adenomatous glands with strong nuclear accumulation of beta-catenin. Even a single adenomatous gland already showed nuclear accumulation of beta-catenin, suggesting that Apc/beta-catenin pathway is an initiating event in gastric tumorigenesis in Apc(Min/+) mice. Myc and cyclin D1 expressions, which are transcriptional targets of beta-catenin/Tcf, increased in the adenomatous lesions. Furthermore, beta-catenin/Tcf reporter transgenic mice with Apc(Min) allele showed higher levels of the transcriptional activity of beta-catenin/Tcf in the gastric tumors. We also treated Apc(Min/+) and wild-type mice with N-methyl-N-nitrosourea (MNU), an alkylating agent that induces adenomas and adenocarcinomas in the stomach. Consequently, MNU-treated Apc(Min/+) mice significantly enhanced the tumor development in comparison with Apc(Min/+) mice or MNU-treated wild-type mice. Several gastric tumors in MNU-treated Apc(Min/+) mice showed invasion into the submucosal layer. These results indicate that the Apc/beta-catenin pathway may play an important role in at least subset of gastric carcinomas. In addition, Apc(Min/+) mice combined with MNU could be a useful short-term model to investigate multistage carcinogenesis in the stomach.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4079-87
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Development of gastric tumors in Apc(Min/+) mice by the activation of the beta-catenin/Tcf signaling pathway.
pubmed:affiliation
Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't