Linked Life Data

14678983

Source:http://linkedlifedata.com/resource/pubmed/id/14678983

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2003-12-17
pubmed:abstractText
Accurate determination of the contributions of oncogenes toward tumor progression requires their regulation. Herein, we created transgenic mice with prostate-specific expression of ligand-inducible FGFR1 or FGFR2, based on lipid-permeable dimerizing molecules, called chemical inducers of dimerization. Despite extensive homology and equivalent expression by both chimeric receptors in the ventral prostate gland, only FGFR1 triggers detectable nuclear translocation of Erk and progression to prostatic intraepithelial neoplasia (PIN). Induction of PIN grade I-II, indicated by multiple layers of atypical cells, is seen consistently by 12 weeks of chemical inducers of dimerization treatment. By 6 months, more extensive nuclear atypia, thickened "reactive" stroma, and basement membrane herniation occurs, corresponding to PIN IV. By timed removal of FGFR1 signaling, we show that induced hyperplasia is reversible until extensive intraductal vascularization occurs, but continued progression requires prolonged FGFR1 signaling. Additionally, by highlighting differences between the two receptors and creating the foundation for controlling FGFR1 signaling during prostate cancer progression, a model of early stage prostate cancer is established for developing targeted intervention directed toward the FGFR signaling axis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
63
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8256-63
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:14678983-Animals, pubmed-meshheading:14678983-Cell Division, pubmed-meshheading:14678983-Disease Progression, pubmed-meshheading:14678983-MAP Kinase Signaling System, pubmed-meshheading:14678983-Male, pubmed-meshheading:14678983-Mice, pubmed-meshheading:14678983-Mice, Transgenic, pubmed-meshheading:14678983-Neovascularization, Pathologic, pubmed-meshheading:14678983-Prostatic Hyperplasia, pubmed-meshheading:14678983-Prostatic Intraepithelial Neoplasia, pubmed-meshheading:14678983-Prostatic Neoplasms, pubmed-meshheading:14678983-Receptor, Fibroblast Growth Factor, Type 1, pubmed-meshheading:14678983-Receptor, Fibroblast Growth Factor, Type 2, pubmed-meshheading:14678983-Receptor Protein-Tyrosine Kinases, pubmed-meshheading:14678983-Receptors, Fibroblast Growth Factor, pubmed-meshheading:14678983-Transgenes
pubmed:year
2003
pubmed:articleTitle
Inducible prostate intraepithelial neoplasia with reversible hyperplasia in conditional FGFR1-expressing mice.
pubmed:affiliation
Department of Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.