Linked Life Data

7794793

Source:http://linkedlifedata.com/resource/pubmed/id/7794793

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1995-8-3
pubmed:abstractText
The tumorigenic phenotype in rat liver epithelial cells overexpressing c-myc may depend on a transforming growth factor (TGF)-alpha/epidermal growth factor receptor autocrine loop (L. W. Lee et al., Cancer Res., 51: 5238-5244, 1991). In the present study, we have used constitutive sense and antisense TGF-alpha expression vectors to modify TGF-alpha production in carcinogen-transformed clonal derivatives of a rat liver epithelial cell line, WB-F344, that variably express c-myc, endogenous TGF-alpha, and tumorigenicity. Transgene-mediated TGF-alpha protein production was elevated 2- to 9-fold in derivatives of a low c-myc-expressing transformed cell line, GN4, and 35-fold in a derivative of a high c-myc-expressing cell line, GN6. Although the GN4- and GN6-derived cell lines expressed functional EGF receptor and steady-state c-myc mRNA levels that were comparable to their respective parental cell lines, increased TGF-alpha expression did not increase the tumorigenicity of the derivatives relative to the parental cell lines. Similarly, in vitro growth characteristics of the GN4- and GN6-derived cell lines were not markedly altered by increased autocrine TGF-alpha production. Additionally, GN4, GN6, and their derivatives were, for the most part, unresponsive to exogenously applied TGF-alpha in vitro. In contrast, antisense TGF-alpha RNA expression significantly suppressed endogenous TGF-alpha production in a high c-myc-expressing, high TGF-alpha-expressing, highly tumorigenic clonal line, GP9; this suppression resulted in lowered steady-state c-myc levels and attenuated in vitro growth. Antisense-mediated suppression of all of these in vitro phenotypes in GP9 was reversed by exogenous TGF-alpha. The latency of tumor formation by the antisense derivative of cell line GP9 was significantly lengthened (> 3-fold) relative to the time required for tumor formation by its parental cell line. These results demonstrate that a TGF-alpha/epidermal growth factor receptor autocrine loop may be necessary for exaggerated in vitro and in vivo growth of some transformed rat liver epithelial cells (e.g., GP9); however, the autocrine loop is not generally sufficient to support tumorigenicity, even in transformed clonal lines expressing elevated levels of c-myc.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1044-9523
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:geneSymbol
c-myc
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
251-61
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:7794793-Actins, pubmed-meshheading:7794793-Animals, pubmed-meshheading:7794793-Blotting, Northern, pubmed-meshheading:7794793-Blotting, Western, pubmed-meshheading:7794793-Carcinogenicity Tests, pubmed-meshheading:7794793-Cell Count, pubmed-meshheading:7794793-Cell Division, pubmed-meshheading:7794793-Cell Line, Transformed, pubmed-meshheading:7794793-Cell Transformation, Neoplastic, pubmed-meshheading:7794793-Gene Expression Regulation, Neoplastic, pubmed-meshheading:7794793-Humans, pubmed-meshheading:7794793-Mice, pubmed-meshheading:7794793-Proto-Oncogene Proteins c-myc, pubmed-meshheading:7794793-RNA, Antisense, pubmed-meshheading:7794793-RNA, Messenger, pubmed-meshheading:7794793-Rats, pubmed-meshheading:7794793-Rats, Inbred F344, pubmed-meshheading:7794793-Receptor, Epidermal Growth Factor, pubmed-meshheading:7794793-Transfection, pubmed-meshheading:7794793-Transforming Growth Factor alpha
pubmed:year
1995
pubmed:articleTitle
Differential dependence of the tumorigenicity of chemically transformed rat liver epithelial cells on autocrine production of transforming growth factor alpha.
pubmed:affiliation
Department of Pathology, School of Medicine, University of North Carolina, Chapel Hill 27599, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.