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.
Matsui
Koshi
K
Second Department of Surgery, University of Toyama, Toyama 930-0194, Japan.
Sugimori
Kazuhito
K
Motomura
Hiraku
H
Ejiri
Naoko
N
Tsukada
Kazuhiro
K
Kitajima
Isao
I
D045744:Cell Line, Tumor; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D020798:Two-Hybrid System Techniques; D050880:p300-CBP Transcription Factors / Q000378:metabolism
D016755:Proto-Oncogene Proteins c-jun; D018719:Erb-b2 Receptor Tyrosine Kinases; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; C065788:transcription factor PEA3