Cdx1 promotes cellular growth of epithelial intestinal cells through induction of the secretory protein PAP I

Eur J Cell Biol. 2001 Feb;80(2):156-63. doi: 10.1078/0171-9335-00148.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / genetics
  • Acute-Phase Proteins / metabolism*
  • Animals
  • Antigens, Neoplasm*
  • Biomarkers, Tumor*
  • Cell Division
  • Cell Line
  • Epithelial Cells / cytology
  • Gene Expression Regulation
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Intestinal Mucosa / cytology*
  • Lectins, C-Type*
  • Mitosis
  • Pancreatitis-Associated Proteins
  • Promoter Regions, Genetic
  • Rats
  • Response Elements
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation


  • Acute-Phase Proteins
  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • CDX1 protein, human
  • Cdx1 protein, rat
  • Homeodomain Proteins
  • Lectins, C-Type
  • Pancreatitis-Associated Proteins
  • REG3A protein, human
  • Reg3b protein, rat
  • Transcription Factors