PMID- 8052651
OWN - NLM
STAT- MEDLINE
DCOM- 19940902
LR  - 20220408
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 91
IP  - 16
DP  - 1994 Aug 2
TI  - A mutant epidermal growth factor receptor common in human glioma confers enhanced 
      tumorigenicity.
PG  - 7727-31
AB  - The development and neoplastic progression of human astrocytic tumors appears to 
      result through an accumulation of genetic alterations occurring in a relatively 
      defined order. One such alteration is amplification of the epidermal growth 
      factor receptor (EGFR) gene. This episomal amplification occurs in 40-50% of 
      glioblastomas, which also normally express endogenous receptors. Moreover, a 
      significant fraction of amplified genes are rearranged to specifically eliminate 
      a DNA fragment containing exons 2-7 of the gene, resulting in an in-frame 
      deletion of 801 bp of the coding sequence of the extracellular domain. Here we 
      used retroviral transfer of such a mutant receptor (de 2-7 EGFR) into 
      glioblastoma cells expressing normal endogenous receptors to test whether the 
      mutant receptor was able to augment their growth and malignancy. Western blotting 
      analysis showed that these cells expressed endogenous EGFR of 170 kDa as well as 
      the exogenous de 2-7 EGFR of 140-155 kDa. Although holo-EGFRs were phosphorylated 
      on tyrosine residues only after exposure of the cells to ligand, de 2-7 EGFRs 
      were constitutively phosphorylated. In tissue culture neither addition of EGF nor 
      expression of the mutant EGFR affected the rate of cell growth. However, when 
      cells expressing mutant EGFR were implanted into nude mice subcutaneously or 
      intracerebrally, tumorigenic capacity was greatly enhanced. These results suggest 
      that a tumor-specific alteration of the EGFR plays a significant role in tumor 
      progression perhaps by influencing interactions of tumor cells with their 
      microenvironment in ways not easily assayed in vitro.
FAU - Nishikawa, R
AU  - Nishikawa R
AD  - Ludwig Institute for Cancer Research, La Jolla, CA 92093-0660.
FAU - Ji, X D
AU  - Ji XD
FAU - Harmon, R C
AU  - Harmon RC
FAU - Lazar, C S
AU  - Lazar CS
FAU - Gill, G N
AU  - Gill GN
FAU - Cavenee, W K
AU  - Cavenee WK
FAU - Huang, H J
AU  - Huang HJ
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Recombinant Proteins)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Brain/pathology
MH  - Cell Transformation, Neoplastic/*genetics
MH  - ErbB Receptors/biosynthesis/*genetics
MH  - Exons/genetics
MH  - Female
MH  - Glioblastoma/*genetics
MH  - Humans
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Neoplasms, Experimental/*genetics
MH  - Phosphorylation
MH  - Recombinant Proteins/biosynthesis
MH  - Tumor Cells, Cultured
PMC - PMC44475
EDAT- 1994/08/02 00:00
MHDA- 1994/08/02 00:01
PMCR- 1995/02/02
CRDT- 1994/08/02 00:00
PHST- 1994/08/02 00:00 [pubmed]
PHST- 1994/08/02 00:01 [medline]
PHST- 1994/08/02 00:00 [entrez]
PHST- 1995/02/02 00:00 [pmc-release]
AID - 10.1073/pnas.91.16.7727 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7727-31. doi: 
      10.1073/pnas.91.16.7727.