Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 153-158 |
| Number of pages | 6 |
| Journal | Oncology Reports |
| Volume | 16 |
| Issue number | 1 |
| DOIs | |
| State | Published - 2006/07 |
Keywords
- Coactivator p300
- HER2/neu
- Polyomavirus enhancer activator 3
- c-Jun
ASJC Scopus subject areas
- Oncology
- Cancer Research