Epithelial-mesenchymal transition (EMT), a crucial event in cancer progression 
and embryonic development, is induced by transforming growth factor (TGF)-beta 
in mouse mammary NMuMG epithelial cells. Id proteins have previously been 
reported to inhibit major features of TGF-beta-induced EMT. In this study, we 
show that expression of the deltaEF1 family proteins, deltaEF1 (ZEB1) and SIP1, 
is gradually increased by TGF-beta with expression profiles reciprocal to that 
of E-cadherin. SIP1 and deltaEF1 each dramatically down-regulated the 
transcription of E-cadherin in NMuMG cells through direct binding to the 
E-cadherin promoter. Silencing of the expression of both SIP1 and deltaEF1, but 
not either alone, completely abolished TGF-beta-induced E-cadherin repression. 
However, expression of mesenchymal markers, including fibronectin, N-cadherin, 
and vimentin, was not affected by knockdown of SIP1 and deltaEF1. 
TGF-beta-induced the expression of Ets1, which in turn activated deltaEF1 
promoter activity. Moreover, up-regulation of SIP1 and deltaEF1 expression by 
TGF-beta was suppressed by knockdown of Ets1 expression. In addition, Id2 
suppressed the TGF-beta- and Ets1-induced up-regulation of deltaEF1. Taken 
together, these findings suggest that the deltaEF1 family proteins, SIP1 and 
deltaEF1, are necessary, but not sufficient, for TGF-beta-induced EMT and that 
Ets1 induced by TGF-beta may function as an upstream transcriptional regulator 
of SIP1 and deltaEF1.