PEA3 cooperates with c-Jun in regulation of HER2/neu transcription
Copyright policy )PEA3 cooperates with c-Jun in regulation of HER2/neu transcription
HER2/neu overexpressing breast tumors exhibit an increase in polyomavirus enhancer activator 3 (PEA3) expression. We examined the relationship between HER2/neu transcriptional activation and PEA3 in cooperation with c-Jun. HER2/neu promoter activity was decreased by deleting PEA3 binding site, and was downregulated when the PEA3 binding site was mutated. PEA3 and c-Jun each weakly enhanced luciferase expression of the HER2/neu promoter. However, the HER2/neu promoter response to PEA3 was considerably enhanced by c-Jun. Thus, we examined the interaction of PEA3 with c-Jun by the two-hybrid system, the transcriptional activity of PEA3 was specifically enhanced by c-Jun. When PEA3, c-Jun and coactivator p300 were cotransfected in MCF7 cells, the transcriptional activity of HER2/neu was increased by up to 20-fold. PEA3 and c-Jun-induced transcription of HER2/neu promoter was repressed by cotransfection of the dominant negative of p300. These results suggest that PEA3 and c-Jun stimulated synergistically the HER2/neu gene transcription with p300.
- University of Toyama Japan
Transcriptional Activation, Transcription, Genetic, Proto-Oncogene Proteins c-jun, Receptor, ErbB-2, Transfection, Gene Expression Regulation, Neoplastic, Cell Line, Tumor, Two-Hybrid System Techniques, Humans, p300-CBP Transcription Factors, Promoter Regions, Genetic, Gene Deletion, Protein Binding, Transcription Factors
Transcriptional Activation, Transcription, Genetic, Proto-Oncogene Proteins c-jun, Receptor, ErbB-2, Transfection, Gene Expression Regulation, Neoplastic, Cell Line, Tumor, Two-Hybrid System Techniques, Humans, p300-CBP Transcription Factors, Promoter Regions, Genetic, Gene Deletion, Protein Binding, Transcription Factors
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