PMID- 8845302
OWN - NLM
STAT- MEDLINE
DCOM- 19961023
LR  - 20220309
IS  - 1044-9523 (Print)
IS  - 1044-9523 (Linking)
VI  - 6
IP  - 10
DP  - 1995 Oct
TI  - Epidermal growth factor ligand-independent, unregulated, cell-transforming 
      potential of a naturally occurring human mutant EGFRvIII gene.
PG  - 1251-9
AB  - 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.
FAU - Batra, S K
AU  - Batra SK
AD  - Duke University Medical Center, Durham, North Carolina 27710, USA.
FAU - Castelino-Prabhu, S
AU  - Castelino-Prabhu S
FAU - Wikstrand, C J
AU  - Wikstrand CJ
FAU - Zhu, X
AU  - Zhu X
FAU - Humphrey, P A
AU  - Humphrey PA
FAU - Friedman, H S
AU  - Friedman HS
FAU - Bigner, D D
AU  - Bigner DD
LA  - eng
GR  - CA 56115/CA/NCI NIH HHS/United States
GR  - NS 20023/NS/NINDS NIH HHS/United States
GR  - NS 29955/NS/NINDS NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cell Growth Differ
JT  - Cell growth & differentiation : the molecular biology journal of the American 
      Association for Cancer Research
JID - 9100024
RN  - 0 (Oncogene Proteins)
RN  - 0 (RNA, Messenger)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Cell Division
MH  - *Cell Transformation, Neoplastic
MH  - Epidermal Growth Factor/metabolism
MH  - ErbB Receptors/*physiology
MH  - Humans
MH  - Kinetics
MH  - Mice
MH  - Mice, Nude
MH  - Oncogene Proteins/physiology
MH  - Phosphorylation
MH  - Protein-Tyrosine Kinases/metabolism
MH  - RNA, Messenger/analysis
MH  - *Sequence Deletion
MH  - Transfection
EDAT- 1995/10/01 00:00
MHDA- 1995/10/01 00:01
CRDT- 1995/10/01 00:00
PHST- 1995/10/01 00:00 [pubmed]
PHST- 1995/10/01 00:01 [medline]
PHST- 1995/10/01 00:00 [entrez]
PST - ppublish
SO  - Cell Growth Differ. 1995 Oct;6(10):1251-9.