BACKGROUND: The epidermal growth factor receptor (EGFR) is expressed at different levels in many cell types and found overexpressed in many cancers. EGFR expression is increased or decreased in response to extracellular stimuli. We examined the effect of increased c-Jun expression on EGFR promoter activity. MATERIALS AND METHODS: We used DNAse I foot-printing analysis to determine the binding of activator protein 1 (AP-1) to the promoter region. We also used cotransfection experiments and western blotting analysis to determine the effect of AP-1 family members on EGFR expression. RESULTS: AP-1 was able to bind to at least seven sites in the EGFR promoter region. Cotransfection of MCF-7 cells with a c-Jun expression vector and the EGFR promoter reporter resulted in a 7-fold increase in promoter activity. JunB, but not c-fos, also enhanced the EGFR promoter activity. An A-Fos-dominant negative shown to inhibit Jun-dependent transactivation was able to prevent c-Jun induction of the promoter activity, but only slightly decreased the basal activity of the promoter. Furthermore, the A-Fos dominant negative was able to inhibit phorbol ester induction of the EGFR promoter. Examination of EGFR expression of MCF-7 stable cell lines that overexpress c-Jun revealed an increase in EGFR expression. Additionally, a cisplatin-resistant cell line, A2780/CP70, which has an increase in AP-1 activity compared with the parental cell line, A2780, was found to have an increase in EGFR level. CONCLUSIONS: These results indicate that AP-1 can act to increase the expression of EGFR and may play a role in upregulation of EGFR in cancer cells.
BACKGROUND: The epidermal growth factor receptor (EGFR) is expressed at different levels in many cell types and found overexpressed in many cancers. EGFR expression is increased or decreased in response to extracellular stimuli. We examined the effect of increased c-Jun expression on EGFR promoter activity. MATERIALS AND METHODS: We used DNAse I foot-printing analysis to determine the binding of activator protein 1 (AP-1) to the promoter region. We also used cotransfection experiments and western blotting analysis to determine the effect of AP-1 family members on EGFR expression. RESULTS:AP-1 was able to bind to at least seven sites in the EGFR promoter region. Cotransfection of MCF-7 cells with a c-Jun expression vector and the EGFR promoter reporter resulted in a 7-fold increase in promoter activity. JunB, but not c-fos, also enhanced the EGFR promoter activity. An A-Fos-dominant negative shown to inhibit Jun-dependent transactivation was able to prevent c-Jun induction of the promoter activity, but only slightly decreased the basal activity of the promoter. Furthermore, the A-Fos dominant negative was able to inhibit phorbol ester induction of the EGFR promoter. Examination of EGFR expression of MCF-7 stable cell lines that overexpress c-Jun revealed an increase in EGFR expression. Additionally, a cisplatin-resistant cell line, A2780/CP70, which has an increase in AP-1 activity compared with the parental cell line, A2780, was found to have an increase in EGFR level. CONCLUSIONS: These results indicate that AP-1 can act to increase the expression of EGFR and may play a role in upregulation of EGFR in cancer cells.
Authors: Antoine Mialon; Matti Sankinen; Henrik Söderström; Teemu T Junttila; Tim Holmström; Riku Koivusalo; Anastassios C Papageorgiou; Randall S Johnson; Sakari Hietanen; Klaus Elenius; Jukka Westermarck Journal: Mol Cell Biol Date: 2005-06 Impact factor: 4.272
Authors: Chong Sun; Liqin Wang; Sidong Huang; Guus J J E Heynen; Anirudh Prahallad; Caroline Robert; John Haanen; Christian Blank; Jelle Wesseling; Stefan M Willems; Davide Zecchin; Sebastijan Hobor; Prashanth K Bajpe; Cor Lieftink; Christina Mateus; Stephan Vagner; Wipawadee Grernrum; Ingrid Hofland; Andreas Schlicker; Lodewyk F A Wessels; Roderick L Beijersbergen; Alberto Bardelli; Federica Di Nicolantonio; Alexander M M Eggermont; Rene Bernards Journal: Nature Date: 2014-03-26 Impact factor: 49.962
Authors: Jason A Wilken; Tayf Badri; Sarah Cross; Rhoda Raji; Alessandro D Santin; Peter Schwartz; Adam J Branscum; Andre T Baron; Adam I Sakhitab; Nita J Maihle Journal: Future Med Chem Date: 2012-03 Impact factor: 3.808
Authors: Konstantin Salnikow; Thomas Kluz; Max Costa; David Piquemal; Zoya N Demidenko; Keping Xie; Mikhail V Blagosklonny Journal: Mol Cell Biol Date: 2002-03 Impact factor: 4.272
Authors: Linda A Scott; J Keith Vass; E Kenneth Parkinson; David A F Gillespie; Joseph N Winnie; Bradford W Ozanne Journal: Mol Cell Biol Date: 2004-02 Impact factor: 4.272