Linked Life Data

10383147

Source:http://linkedlifedata.com/resource/pubmed/id/10383147

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1999-7-19
pubmed:abstractText
Mutations in the transforming growth factor beta type II receptor (TGF-betaRII) have been identified in human cancers, which suggests a causal role for the loss of TGF-betaRII in cancer development. To directly test this in vivo, we have generated transgenic mice expressing a dominant negative TGF-betaRII (delta betaRII) in the epidermis, using a truncated mouse loricrin promoter (ML). ML.delta betaRII transgenic mice exhibited a thickened skin due to epidermal hyperproliferation. When these mice were subjected to a standard two-stage chemical carcinogenesis protocol, they exhibited an increased sensitivity, with an earlier appearance and a 2-fold greater number of papillomas than control mice. In addition, papillomas in control mice regressed after termination of 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment; whereas ML.delta betaRII papillomas progressed to carcinomas. Furthermore, TPA promotion alone induced papilloma formation in ML.delta betaRII mice, which suggests an initiating role for delta betaRII in skin carcinogenesis. ML.delta betaRII tumors also exhibited increased neovascularization and progressed to metastases, although the primary tumors were still classified as carcinoma in situ or well-differentiated carcinomas. Increased expression of vascular endothelial growth factor, an angiogenesis factor, and decreased expression of thrombospondin-1, an angiogenesis inhibitor, were also observed in ML.delta betaRII tumors. The increased angiogenesis correlated with elevated endogenous TGF-beta1 in ML.delta betaRII tumors. These data provide in vivo evidence that inactivation of TGF-betaRII accelerates skin carcinogenesis at both earlier and later stages, and increased angiogenesis is one of the important mechanisms of accelerated tumor growth and metastasis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
59
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2861-8
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:10383147-Animals, pubmed-meshheading:10383147-Carcinogens, pubmed-meshheading:10383147-Epidermis, pubmed-meshheading:10383147-Genes, ras, pubmed-meshheading:10383147-Genetic Predisposition to Disease, pubmed-meshheading:10383147-Humans, pubmed-meshheading:10383147-Mice, pubmed-meshheading:10383147-Mice, Transgenic, pubmed-meshheading:10383147-Neoplasm Metastasis, pubmed-meshheading:10383147-Neovascularization, Pathologic, pubmed-meshheading:10383147-Papilloma, pubmed-meshheading:10383147-Protein-Serine-Threonine Kinases, pubmed-meshheading:10383147-Receptors, Transforming Growth Factor beta, pubmed-meshheading:10383147-Signal Transduction, pubmed-meshheading:10383147-Skin Neoplasms, pubmed-meshheading:10383147-Transforming Growth Factor beta, pubmed-meshheading:10383147-Tumor Suppressor Protein p53
pubmed:year
1999
pubmed:articleTitle
Blocking transforming growth factor beta signaling in transgenic epidermis accelerates chemical carcinogenesis: a mechanism associated with increased angiogenesis.
pubmed:affiliation
Department of Otolaryngology, Baylor College of Medicine, Houston, Texas 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't