PMID- 8895767
OWN - NLM
STAT- MEDLINE
DCOM- 19970106
LR  - 20181130
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 56
IP  - 21
DP  - 1996 Nov 1
TI  - A common mutant epidermal growth factor receptor confers enhanced tumorigenicity 
      on human glioblastoma cells by increasing proliferation and reducing apoptosis.
PG  - 5079-86
AB  - Alterations of the EGFR gene occur frequently in human gliomas where the most 
      common is an in-frame deletion of exons 2-7 from the extracellular domain, 
      resulting in a truncated mutant receptor (deltaEGFR or de 2-7 EGFR). We 
      previously demonstrated that introduction of deltaEGFR into human U87MG 
      glioblastoma cells (U87MG.deltaEGFR) conferred remarkably enhanced tumorigenicity 
      in vivo. Here, we show by cell-mixing experiments that the enhanced 
      tumorigenicity conferred by deltaEGFR is attributable to a growth advantage 
      intrinsic to cells expressing the mutant receptor. We analyzed the labeling index 
      of the proliferation markers Ki-67 and bromodeoxyuridine and found that tumors 
      derived from U87MG.deltaEGFR cells had significantly higher labeling indexes than 
      those of tumors derived from U87MG cells that were either naive, expressed 
      kinase-deficient mutants of deltaEGFR, or overexpressed exogenous wild-type EGFR. 
      We also utilized terminal deoxynucleotidyl transferase-mediated nick end-labeling 
      assays and showed that the apoptotic index of U87MG.deltaEGFR tumors was more 
      than 4-fold lower than that of parental U87MG tumors. This decrease in cell death 
      was inversely correlated with the expression level of Bcl-X(L), a negative 
      regulator of apoptosis, which was more than 3-fold higher in 
      U87MG.deltaEGFR-derived tumors than in those derived from parental cells. Similar 
      observations were obtained in vitro in serum-free conditions. These results 
      suggest that deltaEGFR exerts its pronounced enhancement of glioblastoma 
      tumorigenicity by stimulating proliferation and inhibiting apoptosis and that the 
      effects are directly attributable to its constitutively active signal.
FAU - Nagane, M
AU  - Nagane M
AD  - Ludwig Institute for Cancer Research, University of California at San Diego, La 
      Jolla 92093-0660, USA.
FAU - Coufal, F
AU  - Coufal F
FAU - Lin, H
AU  - Lin H
FAU - Bogler, O
AU  - Bogler O
FAU - Cavenee, W K
AU  - Cavenee WK
FAU - Huang, H J
AU  - Huang HJ
LA  - eng
GR  - 5-T32-NS 07342/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Cell Division
MH  - ErbB Receptors/genetics/*physiology
MH  - Glioblastoma/genetics/*pathology
MH  - Humans
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mutation
MH  - Proto-Oncogene Proteins c-bcl-2/analysis
MH  - Tumor Cells, Cultured
EDAT- 1996/11/01 00:00
MHDA- 1996/11/01 00:01
CRDT- 1996/11/01 00:00
PHST- 1996/11/01 00:00 [pubmed]
PHST- 1996/11/01 00:01 [medline]
PHST- 1996/11/01 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1996 Nov 1;56(21):5079-86.