Linked Life Data

12663497

Source:http://linkedlifedata.com/resource/pubmed/id/12663497

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-3-28
pubmed:abstractText
Sodium butyrate (NaBt) and the pro-apoptotic IGFBP-3 protein, expressed at the top of the normal colonic crypt, have both been implicated in the regulation of apoptosis in colonic epithelial cells. Recent studies in human breast and hepatic cell lines have shown that NaBt can transcriptionally upregulate IGFBP-3 expression. However, the role of butyrate in the regulation of IGFBP-3 expression in the colon is less clear, with reports of both up- and downregulation of the IGFBP-3 protein in colorectal cancer cell lines. In this study we have shown that the level of IGFBP-3 protein expression in colonic epithelial cells correlates with the p53 status of the cells; wildtype p53 cells secrete higher levels of IGFBP3 protein than mutant p53 cell lines. Data presented shows that, when treated with a dose of NaBt that induced significant apoptosis (4 mM for 48 h), there was an upregulation of IGFBP-3 protein in both wildtype and mutant p53 expressing cell lines. The NaBt-induced increase in secreted IGFBP-3 protein was associated with transcriptional upregulation of the IGFBP-3 gene. Using a transfected derivative of the S/RG/C2 adenoma-derived cell line, which stably expressed exogenous IGFBP-3 protein at levels equivalent to that secreted by the 4 mM NaBt-treated parental line (1-3 ng/10(6) cells), we have shown a >2-fold increase in the sensitivity of the cells to NaBt-induced apoptosis when compared with the vector control and parental cell lines. Furthermore, inhibition of the secreted IGFBP-3 protein, by addition of neutralizing antibodies, resulted in a significant decrease in NaBt-induced apoptosis. These data suggest that IGFBP-3 may act as a positive regulator of NaBt-induced apoptosis in colonic epithelial cells, and represents a potentially important mechanism whereby the sensitivity of colonic epithelial cells to NaBt-induced apoptosis can be increased.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
393-401
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Transcriptional upregulation of the insulin-like growth factor binding protein IGFBP-3 by sodium butyrate increases IGF-independent apoptosis in human colonic adenoma-derived epithelial cells.
pubmed:affiliation
CRC Colorectal Tumour Biology Research Group, Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't