Linked Life Data

19760669

Source:http://linkedlifedata.com/resource/pubmed/id/19760669

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2009-11-30
pubmed:abstractText
High levels of insulin-like growth factor-1 (IGF-1) have been associated with a significant increase in colon cancer risk. Additionally, IGF-1 inhibits apoptosis and stimulates proliferation of colonic epithelial cells in vitro. Unfortunately, IGF-1 knockout mice have severe developmental abnormalities and most do not survive, making it difficult to study how genetic ablation of IGF-1 affects colon tumorigenesis. To test the hypothesis that inhibition of IGF-1 prevents colon tumorigenesis, we utilized a preexisting mouse model containing a deletion of the igf1 gene in the liver through a Cre/loxP system. These liver-specific IGF-1 deficient (LID) mice display a 50-75% reduction in circulating IGF-1 levels. We conducted a pilot study to assess the impact of liver-specific IGF-1 deficiency on azoxymethane (AOM)-induced colon tumors. LID mice had a significant inhibition of colon tumor multiplicity in the proximal area of the colon compared to their wild-type littermates. We examined markers of proliferation and apoptosis in the colons of the LID and wild-type mice to see if these were consistent with tumorigenesis. We observed a decrease in proliferation in the colons of the LID mice and an increase in apoptosis. Finally, we examined cytokine levels to determine whether IGF-1 interacts with inflammatory pathways to affect colon tumorigenesis. We observed a significant reduction in the levels of 7 out of 10 cytokines that were measured in the LID mice as compared to wild-type littermates. Results from this pilot study support the hypothesis that reductions in circulating IGF-1 levels may prevent colon tumorigenesis and affect both proliferation and apoptosis. Future experiments will investigate downstream genes of the IGF-1 receptor.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1098-2744
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1071-6
pubmed:dateRevised
2011-3-3
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Genetic reduction of circulating insulin-like growth factor-1 inhibits azoxymethane-induced colon tumorigenesis in mice.
pubmed:affiliation
Laboratory of Human Carcinogenesis, National Cancer Institute, Center for Cancer Research, NIH, Bethesda, Maryland 20892-4258, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't