Linked Life Data

8845302

Source:http://linkedlifedata.com/resource/pubmed/id/8845302

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1996-10-23
pubmed:abstractText
The type III deletion-mutant gene for the epidermal growth factor receptor (EGFRvIII) is frequently expressed in glioblastomas and in breast and non-small cell lung carcinomas. To understand its contribution to the malignant phenotype in humans, we transfected NR6 cells with the mammalian vector pH beta APr-1-neo containing cDNA for either EGFRvIII or wild-type EGFR. Western blot analyses showed that NR6 transfected with wild-type EGFR (NR6W) contained a normal-sized protein (170 kilodaltons); cells transfected with EGFRvIII (NR6M) contained a truncated protein (145 kilodaltons). NR6W cells demonstrated a saturation binding curve with 125I-labeled EGF (affinity, 1.8 x 10(8); r2 = 0.96). NR6M cells, however, showed a low but consistent level of 125I-labeled EGF binding (affinity, 4 x 10(7); r2 = 0.99) compared with NR6, which lacked binding. The population doubling time was shorter for NR6M (0.64 days) than for NR6W (1.1 days) and NR6V (2.27 days). Soft agar focus formation assay by NR6M was 4- to 5-fold higher than that by NR6W. In nude mice, NR6M (1 x 10(7) cells), without exogenous ligand, formed tumors within 12 days; no tumors were observed over 90 days in mice receiving identical doses of NR6W, NR6V, or NR6 cells. EGF stimulated autophosphorylation of receptor in NR6W (4- to 9-fold) but caused only slight (1.8- to 1.9-fold) to no enhancement in NR6M. Further, there was no difference in constitutive tyrosine kinase activity between NR6M and NR6W. Our results clearly indicate that EGFRvIII functions as an oncoprotein, but its intrinsic tyrosine kinase activity may not be responsible for its biological function.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1044-9523
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1251-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Epidermal growth factor ligand-independent, unregulated, cell-transforming potential of a naturally occurring human mutant EGFRvIII gene.
pubmed:affiliation
Duke University Medical Center, Durham, North Carolina 27710, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.