Nuclear epidermal growth factor receptor (EGFR) interacts with signal transducer and activator of transcription 5 (STAT5) in activating Aurora-A gene expression

Liang Yi Hung, Joseph T. Tseng, Yi Chao Lee, Weiya Xia, Ying Nai Wang, Min Li Wu, Yu Hsuan Chuang, Chein Hsien Lai, Wen Chang Chang

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

Loss of the maintenance of genetic material is a critical step leading to tumorigenesis. It was reported that overexpression of Aurora-A and the constitutive activation of the epidermal growth factor (EGF) receptor (EGFR) are implicated in chromosome instability. In this study, we examined that when cells treated with EGF result in centrosome amplification and microtubule disorder, which are critical for genetic instability. Interestingly, the expression of Aurora-A was also increased by EGF stimulus. An immunofluorescence assay indicated that EGF can induce the nuclear translocation of EGFR. Chromatin immunoprecipitation (ChIP) and re-ChIP assays showed significant EGF-induced recruitment of nuclear EGFR and signal transducer and activator of transcription 5 (STAT5) to the Aurora-A promoter. A co-immunoprecipitation assay further demonstrated that EGF induces nuclear interaction between EGFR and STAT5. A small interfering (si)RNA knockdown assay also showed that EGFR and STAT5 are indeed involved in EGF-increased Aurora-A gene expression. Altogether, this study proposes that the nuclear EGFR associates with STAT5 to bind and increase Aurora-A gene expression, which ultimately may lead to chromosome instability and tumorigenesis. The results also provide a novel linkage between the EGFR signaling pathway and overexpression of Aurora-A in tumorigenesis and chromosome instability.

Original languageEnglish
Pages (from-to)4337-4351
Number of pages15
JournalNucleic Acids Research
Volume36
Issue number13
DOIs
Publication statusPublished - Aug 2008
Externally publishedYes

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STAT5 Transcription Factor
Epidermal Growth Factor Receptor
Epidermal Growth Factor
Gene Expression
Chromosomal Instability
Carcinogenesis
Chromatin Immunoprecipitation
Centrosome
Immunoprecipitation
Microtubules
Small Interfering RNA
Fluorescent Antibody Technique
Maintenance

ASJC Scopus subject areas

  • Genetics

Cite this

Nuclear epidermal growth factor receptor (EGFR) interacts with signal transducer and activator of transcription 5 (STAT5) in activating Aurora-A gene expression. / Hung, Liang Yi; Tseng, Joseph T.; Lee, Yi Chao; Xia, Weiya; Wang, Ying Nai; Wu, Min Li; Chuang, Yu Hsuan; Lai, Chein Hsien; Chang, Wen Chang.

In: Nucleic Acids Research, Vol. 36, No. 13, 08.2008, p. 4337-4351.

Research output: Contribution to journalArticle

Hung, Liang Yi ; Tseng, Joseph T. ; Lee, Yi Chao ; Xia, Weiya ; Wang, Ying Nai ; Wu, Min Li ; Chuang, Yu Hsuan ; Lai, Chein Hsien ; Chang, Wen Chang. / Nuclear epidermal growth factor receptor (EGFR) interacts with signal transducer and activator of transcription 5 (STAT5) in activating Aurora-A gene expression. In: Nucleic Acids Research. 2008 ; Vol. 36, No. 13. pp. 4337-4351.
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