Linked Life Data

10023661

Source:http://linkedlifedata.com/resource/pubmed/id/10023661

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1999-2-23
pubmed:abstractText
The precise role of TGF-beta in colorectal carcinogenesis is not clear. The purpose of this study was to determine the phenotypic alterations caused by chronic exposure to TGF-beta in non-transformed intestinal epithelial (RIE-1) cells. Growth of RIE-1 cells was inhibited by >75% following TGF-beta1 treatment for 7 days, after which the cells resumed a normal growth despite the presence of TGF-beta1. These 'TGF-beta-resistant' cells (RIE-Tr) were continuously exposed to TGF-beta for >50 days. Unlike the parental RIE cells, RIE-Tr cells lost contact inhibition, formed foci in culture, grew in soft agarose. RIE-Tr cells demonstrated TGF-beta-dependent invasive potential in an in vitro assay and were resistant to Matrigel and Na-butyrate-induced apoptosis. The RIE-Tr cells were also tumorigenic in nude mice. The transformed phenotype of RIE-Tr cells was associated with a 95% decrease in the level of the type II TGF-beta receptor (TbetaRII) protein, a 40-fold increase in cyclooxygenase-2 (COX-2) protein, and 5.9-fold increase in the production of prostacyclin. Most RIE-Tr subclones that expressed low levels of TbetaRII and high levels of COX-2 were tumorigenic. Those subclones that express abundant TbetaRII and low levels of COX-2 were not tumorigenic in nude mice. A selective COX-2 inhibitor inhibited RIE-Tr cell growth in culture and tumor growth in nude mice. The reduced expression of TbetaRII, increased expression of COX-2, and the ability to form colonies in Matrigel were all reversible upon withdrawal of exogenous TGF-beta1 for the RIE-Tr cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
855-67
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:10023661-Animals, pubmed-meshheading:10023661-Apoptosis, pubmed-meshheading:10023661-Cell Count, pubmed-meshheading:10023661-Cell Division, pubmed-meshheading:10023661-Cell Transformation, Neoplastic, pubmed-meshheading:10023661-Cyclooxygenase 2, pubmed-meshheading:10023661-Down-Regulation, pubmed-meshheading:10023661-Drug Resistance, pubmed-meshheading:10023661-Enzyme Induction, pubmed-meshheading:10023661-Epithelial Cells, pubmed-meshheading:10023661-Intestines, pubmed-meshheading:10023661-Isoenzymes, pubmed-meshheading:10023661-Phenotype, pubmed-meshheading:10023661-Prostaglandin-Endoperoxide Synthases, pubmed-meshheading:10023661-Protein-Serine-Threonine Kinases, pubmed-meshheading:10023661-Rats, pubmed-meshheading:10023661-Receptors, Transforming Growth Factor beta, pubmed-meshheading:10023661-Transforming Growth Factor beta
pubmed:year
1999
pubmed:articleTitle
Transformation of intestinal epithelial cells by chronic TGF-beta1 treatment results in downregulation of the type II TGF-beta receptor and induction of cyclooxygenase-2.
pubmed:affiliation
Department of Surgery, The Vanderbilt Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't