PEA3 TRANSACTIVATES VIMENTIN PROMOTER IN MAMMARY EPITHELIAL AND TUMOR-CELLS

We have used differential display RT-PCR method to detect the genes sp ecifically activated or repressed between mammary tumor and normal mam mary epithelial cells, One of the genes identified is vimentin, The vi mentin gene is abundantly expressed in both human and mouse mammary tu mor cells and its expression decreased dramatically in normal mammary epithelial cells. The expression of vimentin gene correlates with the expression of transcription factor PEA3, Since the promoters of human and mouse vimentin genes contain one PEA3 binding site we investigated the ability of PEA3 to transactivate the vimentin promoter in mouse m ammary epithelial cell CLS1, mouse mammary tumor MMT and human mammary tumor cell lines MCF7 and MDA231, Our results suggest that PEA3 speci fically transactivates vimentin promoter through PEA3 site, Among memb ers of the ETS transcription factor family only Erg showed ability to transactivate vimentin promoter besides PEA3, Our results also suggest that NFkB site on the vimentin promoter may act as positive regulator y element for the transcription of vimentin, In metastatic mammary tum ors derived from mice carrying the polyoma middle T or neu transgene, PEA3 is overexpressed and vimentin has been shown to play a key role i n the motility of cells, Our results suggest that one of the roles of PEA3 in mammary tumor is to participate the activation of vimentin gen e whose gene product in turn contributes to the metastatic potential o f mammary tumors.