| First Author | Howe LR | Year | 2001 |
| Journal | J Biol Chem | Volume | 276 |
| Issue | 23 | Pages | 20108-15 |
| PubMed ID | 11274170 | Mgi Jnum | J:210942 |
| Mgi Id | MGI:5572901 | Doi | 10.1074/jbc.M010692200 |
| Citation | Howe LR, et al. (2001) PEA3 is up-regulated in response to Wnt1 and activates the expression of cyclooxygenase-2. J Biol Chem 276(23):20108-15 |
| abstractText | The inducible prostaglandin synthase cyclooxygenase-2 (COX-2) is aberrantly expressed in intestinal tumors resulting from APC mutation, and is also transcriptionally up-regulated in mouse mammary epithelial cells in response to Wnt1 expression. beta-Catenin stabilization is a consequence of both APC mutation and Wnt signaling. We have previously observed coordinate regulation of the matrilysin promoter by beta-catenin and Ets family transcription factors of the PEA3 subfamily. Here we show that while beta-catenin only weakly activates the COX-2 promoter, PEA3 family transcription factors are potent activators of COX-2 transcription. Consistent with this, PEA3 is up-regulated in Wnt1-expressing mouse mammary epithelial cells, and PEA3 factors are highly expressed in tumors from Wnt1 transgenic mice, in which Cox-2 is also up-regulated. Promoter mapping experiments suggest that the NF-IL6 site in the COX-2 promoter is important for mediating PEA3 responsiveness. The NF-IL6 site is also important for COX-2 transcription in some colorectal cancer lines (Shao, J., Sheng, H., Inoue, H., Morrow, J. D., and DuBois, R. N. (2000) J. Biol. Chem. 275, 33951-33956), and PEA3 factors are highly expressed in colorectal cancer cell lines. Therefore, we speculate that PEA3 factors may contribute to the up-regulation of COX-2 expression resulting from both APC mutation and Wnt1 expression. |
