Negative Regulation of c-Myc Transcription by Pancreas Duodenum Homeobox-1

The pancreatic and duodenal homeobox factor-1 (Pdx1) is essential for pancreatic development and insulin gene transcription, whereas c-Myc has a deleterious effect on islet function. However, the relationship between c-Myc and Pdx1 is poorly concerned. Here we demonstrated that Pdx1 could suppress c-Myc promoter activity, which relied on T cell factor (Tcf) binding elements harbored in c-Myc promoter. Furthermore, the transcription activity of β-catenin/Tcf was markedly decreased on Pdx1 expression, but cotransfection of Pdx1 short hairpin RNA abrogated this effect. Pdx1 expression did not induce β-catenin degradation nor did it alter their subcellular distribution. The mutation analysis showed that the amino acids (1–209) of Pdx1 harboring an inhibitory domain, which might lead to the reduction of β-catenin/Tcf/p300 complex levels and attenuate their binding activity with c-Myc promoter sequences. Moreover, adenovirus-mediated Pdx1 interference caused cell proliferation and cytokine-induced apoptosis via...