Linked Life Data

18790770

Source:http://linkedlifedata.com/resource/pubmed/id/18790770

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2008-9-15
pubmed:abstractText
At later stages of tumor progression, epithelial carcinogenesis is associated with transition to a mesenchymal phenotype, which may contribute to the more aggressive properties of cancer cells and may be stimulated by growth factors such as epidermal growth factor and transforming growth factor-beta. Previously, we found that cells derived from a nodal metastatic squamous cell carcinoma are highly proliferative and motile in vitro and tumorigenic in vivo. In the current study, we have investigated the role of vimentin in proliferation and motility. Cells derived from nodal metastasis express high levels of vimentin, which is undetectable in tumor cells derived from a synchronous primary lesion of tongue. Vimentin expression was enhanced by epidermal growth factor and transforming growth factor-beta both independently and in combination. Use of RNA interference resulted in the generation of stable cell lines that express constitutively low levels of vimentin. RNA interference-mediated vimentin knockdown reduced cellular proliferation, migration, and invasion through a basement membrane substitute by 3-fold compared with nontargeting controls. In addition, cells with reduced vimentin reexpressed differentiation-specific keratins K13, K14, and K15 as a result of increased gene transcription as judged by quantitative PCR and promoter-reporter assays. Furthermore, cells in which vimentin expression was reduced showed a greatly decreased tumorigenic potential, as tumors developing from these cells were 70% smaller than those from control cells. The data suggest that reversal of the mesenchymal phenotype by inhibiting vimentin expression results in reexpression of epithelial characteristics and reduced tumor aggressiveness.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1535-7163
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2894-903
pubmed:meshHeading
pubmed-meshheading:18790770-Animals, pubmed-meshheading:18790770-Carcinoma, Squamous Cell, pubmed-meshheading:18790770-Cell Differentiation, pubmed-meshheading:18790770-Cell Line, Tumor, pubmed-meshheading:18790770-Cell Movement, pubmed-meshheading:18790770-Cell Proliferation, pubmed-meshheading:18790770-Down-Regulation, pubmed-meshheading:18790770-Gene Expression Regulation, Neoplastic, pubmed-meshheading:18790770-Head and Neck Neoplasms, pubmed-meshheading:18790770-Humans, pubmed-meshheading:18790770-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:18790770-Keratins, pubmed-meshheading:18790770-Mice, pubmed-meshheading:18790770-Mice, Nude, pubmed-meshheading:18790770-Neoplasm Metastasis, pubmed-meshheading:18790770-RNA, Messenger, pubmed-meshheading:18790770-RNA, Small Interfering, pubmed-meshheading:18790770-RNA Interference, pubmed-meshheading:18790770-Vimentin
pubmed:year
2008
pubmed:articleTitle
Keratin down-regulation in vimentin-positive cancer cells is reversible by vimentin RNA interference, which inhibits growth and motility.
pubmed:affiliation
Philips Institute, Virginia Commonwealth University, Richmond, Virginia, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't