Linked Life Data

18560355

Source:http://linkedlifedata.com/resource/pubmed/id/18560355

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
43
pubmed:dateCreated
2008-9-26
pubmed:abstractText
The Pas1 locus is the major tumor modifier of lung tumorigenesis in mouse inbred strains. Of six genes contained in a conserved haplotype, three (Casc1, Kras and Ifltd1) have been proposed as Pas1 candidates, but mechanistic evidence is sparse. Herein, we examined urethane-induced lung tumorigenesis in a new mouse model developed by replacing the Kras gene with an Hras gene in the susceptible A/J-type Pas1 locus and crossing these mice with either C57BL/6J or A/J mice. Heterozygous mice carrying the Hras-replacement gene were more susceptible than wild-type mice to lung carcinogenesis, indicating that Hras replacement not only compensates for Kras functions, but is more active. Indeed, most lung tumors carried a Gln61Leu mutation in the Hras-replacement gene, whereas no mutations were observed in the endogenous Hras gene. Thus, the context of the Kras locus determined mutability of ras genes. In mice carrying the Hras-replacement gene, the mutation frequency affecting the wild-type Kras gene was much higher when this gene was located in the A/J type than in the C57BL/6J-type Pas1 locus (12 versus 0%, -log P=5.0). These findings identify cis-acting elements in the Pas1 locus as the functional components controlling genetic susceptibility to lung tumorigenesis by modulating mutability of the Kras gene.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
25
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5753-8
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Cis-acting genomic elements of the Pas1 locus control Kras mutability in lung tumors.
pubmed:affiliation
Department of Experimental Oncology and Laboratories, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't