title: Cdx1 promotes cellular growth of epithelial intestinal cells through induction of the secretory protein PAP I.
abstract: Expression of the Cdx1 homeobox gene in epithelial intestinal cells promotes cellular growth and differentiation. Cdx1and the Pancreatitis Associated Protein I (PAP I) are concomitantly expressed in the epithelial cells of the lower part of the intestinal crypts. Because Cdx1 is a transcription factor and PAP I, in other tissues, is a proliferative factor, we looked for a relationship between these two proteins in the intestinal-derived IEC-6 cells. After stable transfection with a Cdx1 expression vector, they produce high levels of the PAP I transcript and protein indicating a functional link between the two genes. Demonstration of Cdx1 binding to the PAP I promoter region and suppression of PAP I induction after deletion of the corresponding sequence indicated that Cdx1 is a transcription factor controlling PAP I gene expression in intestinal cells. By infecting IEC-6 cells with adenoviruses expressing PAP I, we demonstrated that PAP I induces mitosis in these cells. On the other hand, inhibition of the PAP I expression in the IEC-6 Cdxl-expressing cells using an antisense strategy confirmed the requirement of this protein for the effect of Cdx1 on cell growth. Finally, addition of the immunopurified PAP I to the culture medium promotes cell growth of the IEC-6 cells in a dose-dependent manner. Maximal effect was obtained at 1 ng/ml. Taken together these results demonstrate that PAP I is a target of the Cdx1 homeobox gene in intestinal cells which participates in the regulation of intestinal cell growth via an autocrine and/or paracrine mechanism.
authors: Laboratoire de Recherche de Physiologie et Pathologie Digestives, INSERM U.315, Marseille, France.
authors: V
authors: V
authors: Moucadel
authors: P
authors: P
authors: Soubeyran
authors: S
authors: S
authors: Vasseur
authors: N J
authors: NJ
authors: Dusetti
authors: J C
authors: JC
authors: Dagorn
authors: J L
authors: JL
authors: Iovanna
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002455:Cell Division; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology*; D037181:Lectins, C-Type; D008938:Mitosis; D000073718:Pancreatitis-Associated Proteins; D011401:Promoter Regions, Genetic; D051381:Rats; D020218:Response Elements; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D000209:Acute-Phase Proteins; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C491273:CDX1 protein, human; C491271:Cdx1 protein, rat; D018398:Homeodomain Proteins; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; C000612144:Reg3b protein, rat; D014157:Transcription Factors