Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1995-2-17
pubmed:abstractText
Expression of the T24ras oncogene induces malignancy (tumor growth, invasion and metastasis) in cloned rat embryo fibroblasts (CREF T24). In CREF T24, the rate of phosphorylation of eukaryotic translation initiation factor 4E (eIF-4E) is increased, resulting in increased protein synthesis rates. We have recently shown that reducing the protein levels of eIF-4E in CREF T24 (AS4E line) markedly decreases soft-agar colonization, increases tumor latency periods and increases tumor doubling times without significantly altering monolayer growth. In this study, cells with reduced eIF-4E had delayed and reduced invasiveness and decreased experimental metastasis. Furthermore, reduced eIF-4E levels correlated with decreased expression of the metastasis-associated 92-kDa collagenase type-IV and exon-6 variants of the CD44 adhesion molecule [CD44(6v)]. Reduced eIF-4E levels correlated inversely with increased levels of the putative metastasis-suppressor protein nm23. Cell lines established from AS4E tumors and lung metastases exhibited increased levels of eIF-4E protein and protein synthesis rates compared to the AS4E line. Tumor-derived AS4E had the shortened tumor latency periods of CREF T24 but displayed the slow tumor-growth rates of AS4E. Tumor-derived AS4E exhibited the metastatic capacity of CREF T24 controls. Furthermore, tumor- and lung-nodule-derived AS4E expressed levels of CD44 (6v) and the 92-kDa collagenase type IV comparable to CREF T24 and displayed reduced levels of nm23 relative to AS4E. These results demonstrate that eIF-4E is an important effector molecule involved in oncogenic p21ras-induced malignant transformation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0020-7136
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
60
pubmed:geneSymbol
ras
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
255-63
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:7829225-Animals, pubmed-meshheading:7829225-Cell Line, pubmed-meshheading:7829225-Cell Transformation, Neoplastic, pubmed-meshheading:7829225-Eukaryotic Initiation Factor-4E, pubmed-meshheading:7829225-Fibroblasts, pubmed-meshheading:7829225-Genes, ras, pubmed-meshheading:7829225-Mice, pubmed-meshheading:7829225-Monomeric GTP-Binding Proteins, pubmed-meshheading:7829225-NM23 Nucleoside Diphosphate Kinases, pubmed-meshheading:7829225-Neoplasm Invasiveness, pubmed-meshheading:7829225-Neoplasm Metastasis, pubmed-meshheading:7829225-Nucleoside-Diphosphate Kinase, pubmed-meshheading:7829225-Ornithine Decarboxylase, pubmed-meshheading:7829225-Peptide Initiation Factors, pubmed-meshheading:7829225-Protein Biosynthesis, pubmed-meshheading:7829225-Rats, pubmed-meshheading:7829225-Transcription Factors
pubmed:year
1995
pubmed:articleTitle
Reduction of translation initiation factor 4E decreases the malignancy of ras-transformed cloned rat embryo fibroblasts.
pubmed:affiliation
Department of Microbiology and Immunology, University of Kentucky, L.P. Markey Cancer Center, Lexington.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't