EGFR mutation up-regulates EGR1 expression through the ERK pathway.
BACKGROUND
DelE746_A750-type EGFR is a constitutively active type of mutation that enhances EGFR signaling. However, the changes in gene expression that occur in mutant EGFR-harboring cells has not been fully studied.


METHODS
A gene expression analysis of HEK293 cells transfected with wild-type or mutant EGFR was performed focusing on the significant gene.


RESULTS
Early growth response 1 (EGR1), a transcription factor, was the most strongly up-regulated gene in mutant EGFR-transfected cells among the genes examined. An increase in EGR1 expression in the mutant EGFR cells was confirmed using RT-PCR or immunoblotting. The expression was up-regulated by EGF stimulation and down-regulated by EGFR-tyrosine kinase inhibitor. In addition, the MEK inhibitor U0126 inhibited EGR1 expression, while the phosphatidylinositol 3-kinase inhibitor LY294002 did not.


CONCLUSIONS
Mutant EGFR constitutively up-regulates EGR1 through the ERK pathway, and its expression is correlated with EGFR signal activation. Findings provide an insight into a target gene of mutant EGFR and further improve the understanding of the oncogenic properties of EGFR.
Maegawa
Mari
M
Department of Genome Biology, Kinki University School of Medicine, Osaka 589-8511, Japan.
Arao
Tokuzo
T
Yokote
Hideyuki
H
Matsumoto
Kazuko
K
Kudo
Kanae
K
Tanaka
Kaoru
K
Kaneda
Hiroyasu
H
Fujita
Yoshihiko
Y
Ito
Fumiaki
F
Nishio
Kazuto
K
D002478:Cells, Cultured; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D015151:Immunoblotting; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009154:Mutation / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015854:Up-Regulation
C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D012333:RNA, Messenger; C512478:EGFR protein, human; D066246:ErbB Receptors; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3