EGFR mutation up-regulates EGR1 expression through the ERK pathway.
Anticancer Res
; 29(4): 1111-7, 2009 Apr.
Article
em En
| MEDLINE
| ID: mdl-19414352
ABSTRACT
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. MATERIALS ANDMETHODS:
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.CONCLUSION:
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Proteína Quinase 1 Ativada por Mitógeno
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Proteína Quinase 3 Ativada por Mitógeno
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Proteína 1 de Resposta de Crescimento Precoce
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Receptores ErbB
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Mutação
Limite:
Humans
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article