Regulation of TFF3 expression by homeodomain protein CDX2.
Although trefoil factor family 3 (TFF3) plays an important role in protecting the intestinal mucosa, the regulatory mechanisms of its expression are not fully understood. Since homeodomain protein CDX2 has been reported to be critically involved in the development and differentiation of intestinal epithelium, we examined whether CDX2 affects the expression of TFF3. The transcription of human TFF3 reporter genes was significantly up-regulated by the transient overexpression of CDX2 in COS-7 cells and AGS gastric cells. Electrophoretic mobility shift assay revealed the presence of at least two CDX-binding sites within the human TFF3 promoter. Deletion analysis showed the relative importance of the proximal CDX-binding site at -63. We also detected the up-regulation of endogenous TFF3 mRNA expression in AGS cells stably transfected with CDX2 expression vectors. These results suggest that CDX2 plays a key role in the expression of TFF3 in the intestine and perhaps in intestinal metaplasia of the stomach.
Shimada
Tadahito
T
Department of Gastroenterology, Dokkyo Medical University, Mibu, Tochigi 321-0293, Japan. tshimada@dokkyomed.ac.jp
Koike
Takero
T
Yamagata
Michiko
M
Yoneda
Masashi
M
Hiraishi
Hideyuki
H
D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D000071616:CDX2 Transcription Factor; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D009841:Oligonucleotides / Q000378:metabolism; D010455:Peptides / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D000071165:Trefoil Factor-3
D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; D009841:Oligonucleotides; D010455:Peptides; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C082495:TFF3 protein, human; D000071165:Trefoil Factor-3; D008156:Luciferases