PEA3 Is Up-regulated in Response to Wnt1 and Activates the Expression of Cyclooxygenase-2

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 toWnt1 expression. β-Catenin stabilization is a consequence of both APC mutation and Wnt signaling. We have previously observed coordinate regulation of the matrilysin promoter by β-catenin and Ets family transcription factors of the PEA3 subfamily. Here we show that while β-catenin only weakly activates theCOX-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 whichCox-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 the of COX-2 resulting from mutation and Wnt1 expression. 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 toWnt1 expression. β-Catenin stabilization is a consequence of both APC mutation and Wnt signaling. We have previously observed coordinate regulation of the matrilysin promoter by β-catenin and Ets family transcription factors of the PEA3 subfamily. Here we show that while β-catenin only weakly activates theCOX-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 whichCox-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 the of COX-2 resulting from mutation and Wnt1 expression. cell response mammary Wnt1 is a mammary that a of Wnt1 in mammary in epithelial with R. Wnt1 stabilization of a of and by J. N. β-catenin may transcription Biol. of the Wnt in a consequence of Wnt APC mutation, mutation of of the and β-catenin of Wnt have some of are contribute have by and J. R. we have of mouse mammary epithelial cells regulation of promoter by the inducible of prostaglandin is aberrantly expressed in colorectal and also in tumors from mouse colorectal cancer COX-2 in of the and and J. N. J. J. in mammary is H., and J. Biol. Chem. in is COX-2 a for the of and of COX-2 have in in cancer R. J. J. R. and COX-2 have also in the of colorectal in N. N. J. have for the of COX-2 in in epithelial cells is with and of H., and J. Biol. Chem. in is have of and that also a for in J. J. J. of COX-2 and COX-2 We have previously of in response Wnt1 in mouse mammary epithelial cells The of the the of that COX-2 is also up-regulated in intestinal tumors resulting from APC mutation, we that β-catenin the COX-2 Here we the of both β-catenin and Ets family transcription factors of the PEA3 COX-2 promoter theCOX-2 promoter regulation by The cell for experiments of cells with a β-catenin and with a of the COX-2 promoter J. Biol. Chem. we the of the Ets family transcription PEA3 we previously observed of by PEA3 and β-catenin N. Biol. of β-catenin the of promoter R. J. J. by we observed only of the COX-2 promoter by β-catenin The observed in experiments in response β-catenin PEA3 and PEA3 and β-catenin a response in some experiments the observed for the of PEA3 and β-catenin in the COX-2 promoter of the from cells with for PEA3 β-catenin of and by with PEA3 expressed β-catenin of PEA3 in the COX-2 promoter and that in is the of the COX-2 promoter β-catenin and of β-catenin and PEA3 expression. cells with β-catenin and of in the experiments in and the of β-catenin and of the and by with the and the both PEA3 and β-catenin both are a of with that β-catenin is also the response of the COX-2 promoter the Ets factors and in with the PEA3 and PEA3 the potent of the COX-2 promoter and also of in with the by and of the factors the of the promoter PEA3 in the we that the COX-2 promoter is PEA3 family PEA3 also transcription of the COX-2 of PEA3 cells of COX-2 β-catenin transcription of the the response with the the COX-2 promoter COX-2 promoter is by PEA3 cells with with and cells with the Ets a promoter and a are the of of the by PEA3 cells with of β-catenin and and from cells of by The with for COX-2 and we previously observed cell lines we PEA3 factors a in we observed in response Wnt1 in cells, a mouse mammary epithelial cell PEA3 in cell and also in mammary tumors transgenic We observed in cells in response toWnt1 is with the observed in cells, and a for PEA3 in promoter regulation in this, the of PEA3 and β-catenin COX-2 promoter in cells PEA3 of observed in response β-catenin in experiments by the with cells suggest both in and cells and PEA3 is a potent of the COX-2 promoter PEA3 is up-regulated in cells from and cells and by The with for PEA3 and of PEA3 in mammary and from a mammary from a also from the of of by and with for PEA3 and of PEA3 in the PEA3 in PEA3 in tumors from Wnt1 transgenic from mammary from Wnt1 transgenic and by for PEA3 observed in tumors in tumors transgenic from mammary tumors by for by with and a observed in tumors in of and in a transgenic from a and in with for and of and of the of expressed a and in tumors PEA3 and and of in and mammary of from and from from a mouse by with with and a in a in Wnt1 transgenic in tumors in cells with β-catenin with a COX-2 promoter and with are the of up-regulated in Wnt1-expressing cells, PEA3 highly expressed in tumors transgenic with the in mammary also highly expressed in Wnt1 tumors while in mammary of factors in PEA3 and expressed a in the tumors in mammary of of PEA3 factors in tumors transgenic mice, with the that PEA3 activates the COX-2 promoter, also up-regulated mammary of in mammary from and in tumors from Wnt1 transgenic We observed a in in the tumors with in mammary suggest that of PEA3 factors may contribute in is mammary in from mammary tumors from transgenic and from mammary from from of and for by The of a is by the in the mammary observed in the in the a of promoter in J. Biol. Chem. of the promoter for and the in PEA3 observed The that the PEA3 response and site is in of the promoter, we the PEA3 of promoter the in the NF-IL6 site is of site in the PEA3 we that mutation of the NF-IL6 site and both and promoter mutation of the site PEA3 responsiveness. of the site both and that the of by the the the NF-IL6 site in mediating PEA3 responsiveness. we have previously mutation of the NF-IL6 site have promoter the J. Biol. Chem. we a of the NF-IL6 site in mediating PEA3 the site of PEA3 in the COX-2 promoter and The transcription site is by the is a and transcription of the COX-2 promoter are The of in the in the in are also promoter cells with with the promoter in and with PEA3 are the of of the site in theCOX-2 promoter PEA3 responsiveness. cells with promoter of the COX-2 promoter, with and PEA3 is the promoter the site the NF-IL6 site and the are the of NF-IL6 site is a site for transcription factors of the factors have J. J. Biol. Chem. is with while and are in mediating and cell the of the NF-IL6 site for PEA3 that factors in of theCOX-2 we a Consistent with in cell J. Biol. Chem. J. Biol. Chem. both and COX-2 promoter while promoter of the the response PEA3 a the of a of the PEA3 response of that factors may in mediating COX-2 promoter PEA3 of and the COX-2 cells with of and are the of of the cells with of and with PEA3 are the of of COX-2 previously observed of β-catenin in intestinal tumors and Wnt1-expressing cell lines. The of β-catenin transcription in with transcription factors that β-catenin the COX-2 of we the regulation of by We also the of PEA3 we previously observed coordinate regulation by β-catenin and PEA3 of the matrilysin promoter N. Biol. We observed that β-catenin only of a COX-2 promoter and that are of the promoter are with the by J. Biol. Chem. β-catenin of β-catenin in cells transcription from the suggest is a of and the that β-catenin may COX-2 of transcription the response PEA3 and the factors and the COX-2 promoter and The of that of the COX-2 is the of COX-2 promoter in response Ets family transcription transcription have in regulation of theCOX-2 both NF-IL6 and are important for in mouse cells, and cells in response and J. Biol. Chem. J. Biol. Chem. J. Biol. Chem. of a mouse cell the NF-IL6 and N. J. Biol. Chem. while the site for transcription in response and J. Biol. Chem. J. Biol. Chem. J. Biol. Chem. COX-2 also by stabilization J. J. Biol. Chem. J. J. J. Biol. Chem. we the NF-IL6 site for COX-2 promoter and and of the COX-2 promoter previously for cell J. Biol. Chem. J. Biol. Chem. of PEA3 responsiveness. a both and promoter PEA3 the NF-IL6 in the with PEA3 for the NF-IL6 the NF-IL6 site a PEA3 site of a the NF-IL6 site and of PEA3 a site for are in the of theCOX-2 promoter a PEA3 for by Ets factors and factors have previously J. J. that of and PEA3 may for of COX-2 transcription in we have the that PEA3 the NF-IL6 site Ets in the is the of the COX-2 promoter and is the we have PEA3 responsiveness. the PEA3 in by the of the are the NF-IL6 site is site is from in the J. Biol. Chem. NF-IL6 in the COX-2 promoter have previously in the response J. Biol. Chem. J. Biol. Chem. J. Biol. Chem. N. J. Biol. Chem. NF-IL6 are also in mouse tumors J. Biol. Chem. and of the NF-IL6 site COX-2 promoter in the cancer cell lines and J. J. Biol. Chem. is we have previously PEA3 in intestinal tumors and colorectal cell lines N. Biol. and have also observed COX-2 promoter in colorectal cancer cell lines. and R. regulation of the COX-2 promoter the NF-IL6 may the of site in colorectal cancer lines J. J. Biol. Chem. The and both in intestinal tumors and in Wnt1-expressing cells and tumors and that PEA3 COX-2 in response both Wnt1 and of PEA3 in intestinal tumors resulting from APC mutation and in mammary tumors that PEA3 is a consequence of of the the that PEA3 may a of the of β-catenin a PEA3 promoter that β-catenin in cells PEA3 promoter and J. PEA3 transcription by is of β-catenin transcription in cells, PEA3 and PEA3 by with β-catenin and PEA3 is transcription PEA3 may of PEA3 in the by of the PEA3 of and a in both and the that PEA3 is a of family have the promoter of in with β-catenin N. Biol. matrilysin is in intestinal and matrilysin is also up-regulated in Wnt1-expressing mammary cell lines and R. J. and and matrilysin are Wnt and are by PEA3 we have observed by β-catenin and PEA3 of the R. and in we that the of also is and and the promoter by and and J. speculate that PEA3 factors may contribute regulation of of the Wnt1 is a mammary that a of Wnt1 in mammary in epithelial with R. Wnt1 stabilization of a of and by J. N. β-catenin may transcription Biol. of the Wnt in a consequence of Wnt APC mutation, mutation of of the and β-catenin of Wnt have some of are contribute have by and J. R. we have of mouse mammary epithelial cells regulation of promoter by the inducible of prostaglandin is aberrantly expressed in colorectal and also in tumors from mouse colorectal cancer COX-2 in of the and and J. N. J. J. in mammary is H., and J. Biol. Chem. in is COX-2 a for the of and of COX-2 have in in cancer R. J. J. R. and COX-2 have also in the of colorectal in N. N. J. have for the of COX-2 in in epithelial cells is with and of H., and J. Biol. Chem. in is have of and that also a for in J. J. J. of COX-2 and COX-2 We have previously of in response Wnt1 in mouse mammary epithelial cells The of the the of that COX-2 is also up-regulated in intestinal tumors resulting from APC mutation, we that β-catenin the COX-2 Here we the of both β-catenin and Ets family transcription factors of the PEA3 COX-2 promoter theCOX-2 promoter regulation by The cell for experiments of cells with a β-catenin and with a of the COX-2 promoter J. Biol. Chem. we the of the Ets family transcription PEA3 we previously observed of by PEA3 and β-catenin N. Biol. of β-catenin the of promoter R. J. J. by we observed only of the COX-2 promoter by β-catenin The observed in experiments in response β-catenin PEA3 and PEA3 and β-catenin a response in some experiments the observed for the of PEA3 and β-catenin in the COX-2 promoter of the from cells with for PEA3 β-catenin of and by with PEA3 expressed β-catenin of PEA3 in the COX-2 promoter and that in is the of the COX-2 promoter β-catenin and also the response of the COX-2 promoter the Ets factors and in with the PEA3 and PEA3 the potent of the COX-2 promoter and also of in with the by and of the factors the of the promoter PEA3 in the we that the COX-2 promoter is PEA3 family PEA3 also transcription of the COX-2 of PEA3 cells of COX-2 β-catenin transcription of the the response with the the COX-2 promoter COX-2 promoter is by PEA3 cells with with and cells with the Ets a promoter and a are the of of the by PEA3 cells with of β-catenin and and from cells of by The with for COX-2 and we previously observed cell lines we PEA3 factors a in we observed in response Wnt1 in cells, a mouse mammary epithelial cell PEA3 in cell and also in mammary tumors transgenic We observed in cells in response toWnt1 is with the observed in cells, and a for PEA3 in promoter regulation in this, the of PEA3 and β-catenin COX-2 promoter in cells PEA3 of observed in response β-catenin in experiments by the with cells suggest both in and cells and PEA3 is a potent of the COX-2 promoter PEA3 is up-regulated in cells from and cells and by The with for PEA3 and of PEA3 in mammary and from a mammary from a also from the of of by and with for PEA3 and of PEA3 in the PEA3 in PEA3 in tumors from Wnt1 transgenic from mammary from Wnt1 transgenic and by for PEA3 observed in tumors in tumors transgenic from mammary tumors by for by with and a observed in tumors in of and in a transgenic from a and in with for and of and of the of expressed a and in tumors PEA3 and and of in and mammary of from and from from a mouse by with with and a in a in Wnt1 transgenic in tumors in cells with β-catenin with a COX-2 promoter and with are the of up-regulated in Wnt1-expressing cells, PEA3 highly expressed in tumors transgenic with the in mammary also highly expressed in Wnt1 tumors while in mammary of factors in PEA3 and expressed a in the tumors in mammary of of PEA3 factors in tumors transgenic mice, with the that PEA3 activates the COX-2 promoter, also up-regulated mammary of in mammary from and in tumors from Wnt1 transgenic We observed a in in the tumors with in mammary suggest that of PEA3 factors may contribute in is mammary in from mammary tumors from transgenic and from mammary from from of and for by The of a is by the in the mammary observed in the in the a of promoter in J. Biol. Chem. of the promoter for and the in PEA3 observed The that the PEA3 response and site is in of the promoter, we the PEA3 of promoter the in the NF-IL6 site is of site in the PEA3 we that mutation of the NF-IL6 site and both and promoter mutation of the site PEA3 responsiveness. of the site both and that the of by the the the NF-IL6 site in mediating PEA3 responsiveness. we have previously mutation of the NF-IL6 site have promoter the J. Biol. Chem. we a of the NF-IL6 site in mediating PEA3 the site of PEA3 in the COX-2 promoter and The transcription site is by the is a and transcription of the COX-2 promoter are The of in the in the in are also promoter cells with with the promoter in and with PEA3 are the of of the site in theCOX-2 promoter PEA3 responsiveness. cells with promoter of the COX-2 promoter, with and PEA3 is the promoter the site the NF-IL6 site and the are the of NF-IL6 site is a site for transcription factors of the factors have J. J. Biol. Chem. is with while and are in mediating and cell the of the NF-IL6 site for PEA3 that factors in of theCOX-2 we a Consistent with in cell J. Biol. Chem. J. Biol. Chem. both and COX-2 promoter while promoter of the the response PEA3 a the of a of the PEA3 response of that factors may in mediating COX-2 promoter PEA3 of and the COX-2 cells with of and are the of of the cells with of and with PEA3 are the of theCOX-2 promoter regulation by The cell for experiments of cells with a β-catenin and with a of the COX-2 promoter J. Biol. Chem. we the of the Ets family transcription PEA3 we previously observed of by PEA3 and β-catenin N. Biol. of β-catenin the of promoter R. J. J. by we observed only of the COX-2 promoter by β-catenin The observed in experiments in response β-catenin PEA3 and PEA3 and β-catenin a response in some experiments the observed for the of PEA3 and β-catenin in the COX-2 promoter of the from cells with for PEA3 β-catenin of and by with PEA3 expressed β-catenin of PEA3 in the COX-2 promoter and that in is the of the COX-2 promoter β-catenin and We also the response of the COX-2 promoter the Ets factors and in with the PEA3 and PEA3 the potent of the COX-2 promoter and also of in with the by and of the factors the of the promoter PEA3 in the we that the COX-2 promoter is PEA3 family PEA3 also transcription of the COX-2 of PEA3 cells of COX-2 β-catenin transcription of the the response with the the COX-2 promoter we previously observed cell lines we PEA3 factors a in we observed in response Wnt1 in cells, a mouse mammary epithelial cell PEA3 in cell and also in mammary tumors transgenic We observed in cells in response toWnt1 is with the observed in cells, and a for PEA3 in promoter regulation in this, the of PEA3 and β-catenin COX-2 promoter in cells PEA3 of observed in response β-catenin in experiments by the with cells suggest both in and cells and PEA3 is a potent of the COX-2 promoter up-regulated in Wnt1-expressing cells, PEA3 highly expressed in tumors transgenic with the in mammary also highly expressed in Wnt1 tumors while in mammary of factors in PEA3 and expressed a in the tumors in mammary of of PEA3 factors in tumors transgenic mice, with the that PEA3 activates the COX-2 promoter, also up-regulated mammary of in mammary from and in tumors from Wnt1 transgenic We observed a in in the tumors with in mammary suggest that of PEA3 factors may contribute in the in the a of promoter in J. Biol. Chem. of the promoter for and the in PEA3 observed The that the PEA3 response and site is in of the promoter, we the PEA3 of promoter the in the NF-IL6 site is of site in the PEA3 we that mutation of the NF-IL6 site and both and promoter mutation of the site PEA3 responsiveness. of the site both and that the of by the the the NF-IL6 site in mediating PEA3 responsiveness. we have previously mutation of the NF-IL6 site have promoter the J. Biol. Chem. we a of the NF-IL6 site in mediating PEA3 responsiveness. The NF-IL6 site is a site for transcription factors of the factors have J. J. Biol. Chem. is with while and are in mediating and cell the of the NF-IL6 site for PEA3 that factors in of theCOX-2 we a Consistent with in cell J. Biol. Chem. J. Biol. Chem. both and COX-2 promoter while promoter of the the response PEA3 a the of a of the PEA3 response of that factors may in mediating COX-2 promoter PEA3 of COX-2 previously observed of β-catenin in intestinal tumors and Wnt1-expressing cell lines. The of β-catenin transcription in with transcription factors that β-catenin the COX-2 of we the regulation of by We also the of PEA3 we previously observed coordinate regulation by β-catenin and PEA3 of the matrilysin promoter N. Biol. We observed that β-catenin only of a COX-2 promoter and that are of the promoter are with the by J. Biol. Chem. β-catenin of β-catenin in cells transcription from the suggest is a of and the that β-catenin may COX-2 of transcription the response PEA3 and the factors and the COX-2 promoter and The of that of the COX-2 is the of COX-2 promoter in response Ets family transcription transcription have in regulation of theCOX-2 both NF-IL6 and are important for in mouse cells, and cells in response and J. Biol. Chem. J. Biol. Chem. J. Biol. Chem. of a mouse cell the NF-IL6 and N. J. Biol. Chem. while the site for transcription in response and J. Biol. Chem. J. Biol. Chem. J. Biol. Chem. COX-2 also by stabilization J. J. Biol. Chem. J. J. J. Biol. Chem. we the NF-IL6 site for COX-2 promoter and and of the COX-2 promoter previously for cell J. Biol. Chem. J. Biol. Chem. of PEA3 responsiveness. a both and promoter PEA3 the NF-IL6 in the with PEA3 for the NF-IL6 the NF-IL6 site a PEA3 site of a the NF-IL6 site and of PEA3 a site for are in the of theCOX-2 promoter a PEA3 for by Ets factors and factors have previously J. J. that of and PEA3 may for of COX-2 transcription in we have the that PEA3 the NF-IL6 site NF-IL6 in the COX-2 promoter have previously in the response J. Biol. Chem. J. Biol. Chem. J. Biol. Chem. N. J. Biol. Chem. NF-IL6 are also in mouse tumors J. Biol. Chem. and of the NF-IL6 site COX-2 promoter in the cancer cell lines and J. J. Biol. Chem. is we have previously PEA3 in intestinal tumors and colorectal cell lines N. Biol. and have also observed COX-2 promoter in colorectal cancer cell lines. and R. regulation of the COX-2 promoter the NF-IL6 may the of site in colorectal cancer lines J. J. Biol. Chem. The and both in intestinal tumors and in Wnt1-expressing cells and tumors and that PEA3 COX-2 in response both Wnt1 and of PEA3 in intestinal tumors resulting from APC mutation and in mammary tumors that PEA3 is a consequence of of the the that PEA3 may a of the of β-catenin a PEA3 promoter that β-catenin in cells PEA3 promoter and J. PEA3 transcription by is of β-catenin transcription in cells, PEA3 and PEA3 by with β-catenin and PEA3 is transcription PEA3 may of PEA3 in the by of the PEA3 of and a in both and the that PEA3 is a of family have the promoter of in with β-catenin N. Biol. matrilysin is in intestinal and matrilysin is also up-regulated in Wnt1-expressing mammary cell lines and R. J. and and matrilysin are Wnt and are by PEA3 we have observed by β-catenin and PEA3 of the R. and in we that the of also is and and the promoter by and and J. speculate that PEA3 factors may contribute regulation of of the of COX-2 previously observed of β-catenin in intestinal tumors and Wnt1-expressing cell lines. The of β-catenin transcription in with transcription factors that β-catenin the COX-2 of we the regulation of by We also the of PEA3 we previously observed coordinate regulation by β-catenin and PEA3 of the matrilysin promoter N. Biol. We observed that β-catenin only of a COX-2 promoter and that are of the promoter are with the by J. Biol. Chem. β-catenin of β-catenin in cells transcription from the suggest is a of and the that β-catenin may COX-2 of transcription the response PEA3 and the factors and the COX-2 promoter and The of that of the COX-2 is the of COX-2 promoter in response Ets family transcription transcription have in regulation of theCOX-2 both NF-IL6 and are important for in mouse cells, and cells in response and J. Biol. Chem. J. Biol. Chem. J. Biol. Chem. of a mouse cell the NF-IL6 and N. J. Biol. Chem. while the site for transcription in response and J. Biol. Chem. J. Biol. Chem. J. Biol. Chem. COX-2 also by stabilization J. J. Biol. Chem. J. J. J. Biol. Chem. we the NF-IL6 site for COX-2 promoter and and of the COX-2 promoter previously for cell J. Biol. Chem. J. Biol. Chem. of PEA3 responsiveness. a both and promoter PEA3 the NF-IL6 in the with PEA3 for the NF-IL6 the NF-IL6 site a PEA3 site of a the NF-IL6 site and of PEA3 a site for are in the of theCOX-2 promoter a PEA3 for by Ets factors and factors have previously J. J. that of and PEA3 may for of COX-2 transcription in we have the that PEA3 the NF-IL6 site NF-IL6 in the COX-2 promoter have previously in the response J. Biol. Chem. J. Biol. Chem. J. Biol. Chem. N. J. Biol. Chem. NF-IL6 are also in mouse tumors J. Biol. Chem. and of the NF-IL6 site COX-2 promoter in the cancer cell lines and J. J. Biol. Chem. is we have previously PEA3 in intestinal tumors and colorectal cell lines N. Biol. and have also observed COX-2 promoter in colorectal cancer cell lines. and R. regulation of the COX-2 promoter the NF-IL6 may the of site in colorectal cancer lines J. J. Biol. Chem. The and both in intestinal tumors and in Wnt1-expressing cells and tumors and that PEA3 COX-2 in response both Wnt1 and The of PEA3 in intestinal tumors resulting from APC mutation and in mammary tumors that PEA3 is a consequence of of the the that PEA3 may a of the of β-catenin a PEA3 promoter that β-catenin in cells PEA3 promoter and J. PEA3 transcription by is of β-catenin transcription in cells, PEA3 and PEA3 by with β-catenin and PEA3 is transcription PEA3 may of PEA3 in the by of the PEA3 of and a in both and the that PEA3 is a of PEA3 family have the promoter of in with β-catenin N. Biol. matrilysin is in intestinal and matrilysin is also up-regulated in Wnt1-expressing mammary cell lines and R. J. and and matrilysin are Wnt and are by PEA3 we have observed by β-catenin and PEA3 of the R. and in we that the of also is and and the promoter by and and J. speculate that PEA3 factors may contribute regulation of of the We for and for We R. R. and for of

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