Linked Life Data

18000371

Source:http://linkedlifedata.com/resource/pubmed/id/18000371

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-4
pubmed:dateCreated
2007-11-16
pubmed:abstractText
FHIT, at a constitutively active chromosome fragile site, is often a target of chromosomal aberrations and deletion in a large fraction of human tumors. Inactivation of murine Fhit allelessignificantly increases susceptibility of mice to spontaneous and carcinogen-induced tumorigenesis. In this study, transgenic mice, carrying a human FHIT cDNA under control of the endogenous promoter, were produced to determine the effect of Fhit expression, from a nonfragile cDNA transgene outside the fragile region, on carcinogen-induced tumor susceptibility of wildtype and Fhit heterozygous mice. Mice received sufficient oral doses of N-nitrosomethybenzylamine (NMBA) to cause forestomach tumors in >80% of nontransgenic control mice. Although the level of expression of the FHIT transgene in the recombinant mouse strains was much lower than the level of endogenous Fhit expression, the tumor burden in NMBA-treated male transgenic mice was significantly reduced, while female transgenic mice were not protected. To determine if the difference in protection could be due to differences in epigenetic changes at the transgene loci in male versus female mice, we examined expression, hypermethylation and induced re-expression of FHIT transgenes in male and female mice or cells derived from them. The transgene was methylated in male and female mice and in cell lines established from male and female transgenic kidneys, the FHIT locus was both hypermethylated and deacetylated. It is likely that the FHIT transgene is more tightly silenced in female transgenic mice, leading to a lack of protection from tumor induction.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1424-859X
pubmed:author
pubmed:copyrightInfo
Copyright (c) 2007 S. Karger AG, Basel.
pubmed:issnType
Electronic
pubmed:volume
118
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
196-203
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18000371-Acid Anhydride Hydrolases, pubmed-meshheading:18000371-Animals, pubmed-meshheading:18000371-Base Sequence, pubmed-meshheading:18000371-Blotting, Western, pubmed-meshheading:18000371-Carcinogens, pubmed-meshheading:18000371-DNA Methylation, pubmed-meshheading:18000371-DNA Modification Methylases, pubmed-meshheading:18000371-DNA Primers, pubmed-meshheading:18000371-Female, pubmed-meshheading:18000371-Genetic Predisposition to Disease, pubmed-meshheading:18000371-Histone Deacetylase Inhibitors, pubmed-meshheading:18000371-In Situ Hybridization, Fluorescence, pubmed-meshheading:18000371-Male, pubmed-meshheading:18000371-Mice, pubmed-meshheading:18000371-Mice, Transgenic, pubmed-meshheading:18000371-Neoplasm Proteins, pubmed-meshheading:18000371-Neoplasms, Experimental, pubmed-meshheading:18000371-Promoter Regions, Genetic, pubmed-meshheading:18000371-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:18000371-Transgenes
pubmed:year
2007
pubmed:articleTitle
Influence of a nonfragile FHIT transgene on murine tumor susceptibility.
pubmed:affiliation
Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
pubmed:publicationType
Journal Article