Linked Life Data

17637743

Source:http://linkedlifedata.com/resource/pubmed/id/17637743

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-1-17
pubmed:abstractText
Transforming growth factor-beta (TGF-beta) is overexpressed at sites of wound repair and in most adenocarcinomas including prostate cancer. In stromal tissues, TGF-beta regulates cell proliferation, phenotype and matrix synthesis. To address mechanisms of TGF-beta action in cancer-associated reactive stroma, we developed prostate stromal cells null for TGF-beta receptor II (TbetaRII) or engineered to express a dominant-negative Smad3 to attenuate TGF-beta signaling. The differential reactive stroma (DRS) xenograft model was used to evaluate altered stromal TGF-beta signaling on LNCaP tumor progression. LNCaP xenograft tumors constructed with TbetaRII null or dominant-negative Smad3 stromal cells exhibited a significant reduction in mass and microvessel density relative to controls. Additionally, decreased cellular fibroblast growth factor-2 (FGF-2) immunostaining was associated with attenuated TGF-beta signaling in stroma. In vitro, TGF-beta stimulated stromal FGF-2 expression and release. However, stromal cells with attenuated TGF-beta signaling were refractory to TGF-beta-stimulated FGF-2 expression and release. Re-expression of FGF-2 in these stromal cells in DRS xenografts resulted in restored tumor mass and microvessel density. In summary, these data show that TGF-beta signaling in reactive stroma is angiogenic and tumor promoting and that this effect is mediated in part through a TbetaRII/Smad3-dependent upregulation of FGF-2 expression and release.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
17
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
450-9
pubmed:meshHeading
pubmed-meshheading:17637743-Animals, pubmed-meshheading:17637743-Carcinoma, pubmed-meshheading:17637743-Disease Progression, pubmed-meshheading:17637743-Fibroblast Growth Factor 2, pubmed-meshheading:17637743-Gene Expression Regulation, Neoplastic, pubmed-meshheading:17637743-Humans, pubmed-meshheading:17637743-Male, pubmed-meshheading:17637743-Mice, pubmed-meshheading:17637743-Mice, Inbred C57BL, pubmed-meshheading:17637743-Mice, Nude, pubmed-meshheading:17637743-Neovascularization, Pathologic, pubmed-meshheading:17637743-Prostatic Neoplasms, pubmed-meshheading:17637743-Protein-Serine-Threonine Kinases, pubmed-meshheading:17637743-Receptors, Transforming Growth Factor beta, pubmed-meshheading:17637743-Signal Transduction, pubmed-meshheading:17637743-Stromal Cells, pubmed-meshheading:17637743-Transforming Growth Factor beta, pubmed-meshheading:17637743-Transplantation, Heterologous, pubmed-meshheading:17637743-Tumor Cells, Cultured
pubmed:year
2008
pubmed:articleTitle
Fibroblast growth factor-2 mediates transforming growth factor-beta action in prostate cancer reactive stroma.
pubmed:affiliation
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural