Linked Life Data

9223663

Source:http://linkedlifedata.com/resource/pubmed/id/9223663

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
25
pubmed:dateCreated
1997-8-7
pubmed:abstractText
Basic Fibroblast Growth Factor (bFGF/FGF2) is thought to play a decisive role in malignant progression. Aberrant expression of bFGF causes constitutive autocrine activation of its cognate receptor and autonomous growth of human melanoma cells or bFGF transformed fibroblasts in culture. It remains to be determined, however, whether the endogenous bFGF confers growth advantage to tumors and what are the downstream targets of the activated FGF receptor critical for its transforming capacity. We therefore transfected metastatic melanoma cells and bFGF transformed mouse fibroblasts with a dominant-negative mutant of the murine FGF receptor 1 (fgfr1/flg), comprising the extracellular and transmembrane domains but lacking the intracellular kinase domain (dnflg). Reverse transcriptase-PCR, 125I-bFGF binding and affinity labeling analyses show that the truncated receptor is targeted to the membrane and is expressed at much higher levels than the endogenous receptor in all of the selected clones. Expression of the dnflg dramatically reduces the basal as well as bFGF induced growth of these cells in vitro and also suppresses their tumorigenic potential in nude mice. The expression of the dnflg does not significantly alter the general level of tyrosyl-phosphorylated proteins in the trunsduced melanoma cells. Rather, a major downstream affected target is a Src-family kinase, whose activity, determined by an in vitro immune kinase assay, is stimulated in normal melanocytes by exogenous bFGF, and is markedly reduced in the dnflg-expressing melanoma cells. The present study demonstrates that direct interference with the activity of FGF receptors has a deleterious effect on cell proliferation and survival in vitro and in vivo leading to the suppression of melanoma tumor progression possibly through the inactivation of a Src-family kinase.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2999-3009
pubmed:dateRevised
2010-5-26
pubmed:meshHeading
pubmed-meshheading:9223663-3T3 Cells, pubmed-meshheading:9223663-Animals, pubmed-meshheading:9223663-Cell Division, pubmed-meshheading:9223663-Cell Line, Transformed, pubmed-meshheading:9223663-Fibroblast Growth Factor 2, pubmed-meshheading:9223663-Fibroblasts, pubmed-meshheading:9223663-Genes, Dominant, pubmed-meshheading:9223663-Humans, pubmed-meshheading:9223663-Melanoma, pubmed-meshheading:9223663-Mice, pubmed-meshheading:9223663-Phenotype, pubmed-meshheading:9223663-Protein-Tyrosine Kinases, pubmed-meshheading:9223663-Receptor, Fibroblast Growth Factor, Type 1, pubmed-meshheading:9223663-Receptor Protein-Tyrosine Kinases, pubmed-meshheading:9223663-Receptors, Fibroblast Growth Factor, pubmed-meshheading:9223663-Recombinant Proteins, pubmed-meshheading:9223663-Tumor Cells, Cultured, pubmed-meshheading:9223663-src Homology Domains
pubmed:year
1997
pubmed:articleTitle
Suppression of autocrine cell proliferation and tumorigenesis of human melanoma cells and fibroblast growth factor transformed fibroblasts by a kinase-deficient FGF receptor 1: evidence for the involvement of Src-family kinases.
pubmed:affiliation
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't