Linked Life Data

10469614

Source:http://linkedlifedata.com/resource/pubmed/id/10469614

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1999-9-30
pubmed:abstractText
The colorectal mucosa of pre-symptomatic individuals with familial adenomatous polyposis (FAP) contains elevated levels of the proliferation-associated polyamines. The Min mouse, like humans with FAP, expresses an abnormal genotype for the APC tumor suppressor gene. In order to determine how APC mutation influences intestinal tissue polyamine content, we measured steady-state RNA levels of ornithine decarboxylase (ODC), the first enzyme in polyamine synthesis, antizyme (AZ), a protein which negatively regulates ODC, and the spermidine/spermine N(1)-acetyltransferase (SSAT), the first enzyme in polyamine catabolism. RNA content was increased 6- to 8-fold in both the small intestine and colon for ODC, decreased significantly in the small intestine but not the colon for AZ and was not statistically different in either intestinal tissue for SSAT in Min mice compared with normal littermates. Consistent with the changes in ODC and AZ gene expression, small intestinal, but not colonic, polyamine content was elevated in Min mice compared with normal littermates. Treatment of Min mice with the specific ODC inhibitor difluoromethylornithine (DFMO) suppressed small intestinal, but not colonic, polyamine content and tumor number. These data indicate that small intestinal tissue polyamine content is elevated in Min mice by a mechanism involving APC-dependent changes in ODC and AZ RNA. Further, ODC enzyme activity, which is influenced by both ODC and AZ RNA levels and inhibited by DFMO, is consequential for small intestinal tumorigenesis in this model. In the FAP population, DFMO may be of value in the chemoprevention of small intestinal adenocarcinoma that remains a risk following colectomy.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1709-13
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10469614-Acetyltransferases, pubmed-meshheading:10469614-Animals, pubmed-meshheading:10469614-Anticarcinogenic Agents, pubmed-meshheading:10469614-Colon, pubmed-meshheading:10469614-Colonic Neoplasms, pubmed-meshheading:10469614-Eflornithine, pubmed-meshheading:10469614-Gene Expression Regulation, pubmed-meshheading:10469614-Genes, APC, pubmed-meshheading:10469614-Intestinal Mucosa, pubmed-meshheading:10469614-Intestinal Neoplasms, pubmed-meshheading:10469614-Intestine, Small, pubmed-meshheading:10469614-Mice, pubmed-meshheading:10469614-Mice, Inbred C57BL, pubmed-meshheading:10469614-Mice, Mutant Strains, pubmed-meshheading:10469614-Organ Specificity, pubmed-meshheading:10469614-Ornithine Decarboxylase, pubmed-meshheading:10469614-Polyamines, pubmed-meshheading:10469614-Protein Biosynthesis, pubmed-meshheading:10469614-Proteins, pubmed-meshheading:10469614-RNA, Messenger
pubmed:year
1999
pubmed:articleTitle
APC-dependent changes in expression of genes influencing polyamine metabolism, and consequences for gastrointestinal carcinogenesis, in the Min mouse.
pubmed:affiliation
Department of Radiation Oncology, Arizona Cancer Center and Steele Memorial Children's Research Center, The University of Arizona, Tucson, AZ 5724, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't