Figure 6

ZEB1 as a constitutive repressor of the CAR promoter in PANC-1 cells. Our data supports a model in which ZEB1 constitutively binds to E2 box 1 (Fig. 4B) in the human CAR promoter thereby controlling the basal levels of CAR. TGF-β may further repress the promoter via E2 box 2 and its adjacent Smad-binding element (SBE) by a mechanism likely involving Snail-Smad3/4 [37]. Knockdown of ZEB1 increases CAR expression despite the presence of Snail-Smad3/4. Factors binding to the ETS-CRE region (Fig. 1C), here speculatively indicated as ETS or CREB, strongly induce CAR expression ("+++"), while ZEB1 and Snail-Smad3/4 negatively ("-") regulate the CAR promoter. Net CAR expression indicates overall promoter activity. See text for details.