Linked Life Data

12907606

Source:http://linkedlifedata.com/resource/pubmed/id/12907606

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2003-8-8
pubmed:abstractText
The adenomatous polyposis coli (APC) gene, a member of the WNT pathway, has been shown to assign intestinal epithelial cells to a program of proliferation or differentiation through regulation of the beta-catenin/TCF-4 complex. Wild-type APC, in certain cellular contexts, appears to induce differentiation and apoptosis, although mutant forms of APC, known to produce polyps and ultimately cancers, may suppress these events. Here, we show that mutant forms of APC can induce repression of select terminal caspases as a potential means of attenuating responses to apoptotic stimuli. Using gene expression profiling to interrogate the intact intestines of Apc(+/min) mice harboring numerous polyps, we identified a reduction in the mRNA expression of both caspases 3 and 7. We additionally identified a reduction in protein levels of caspase-3, caspase-7, and caspase-9 in human colon cancer specimens known to harbor APC mutations. A reduction in caspase protein levels resulted in resistance to apoptotic-inducing agents and restoration of caspase levels reinstated apoptotic capacities. Consistent with Wnt pathway involvement, dominant negative TCF/LEF induced caspase protein expression. These data provide support for the hypothesis that one of the functions of APC is the regulation of caspase activity and other apoptotic proteins by controlling their expression levels in the cell.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
63
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4368-74
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Regulation of caspase expression and apoptosis by adenomatous polyposis coli.
pubmed:affiliation
Department of Interdisciplinary Oncology and Surgery, University of South Florida, Tampa, FL 33612, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.