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

Authors: Moucadel V.1; Soubeyran P.1; Vasseur S.1; Dusetti N.J.1; Dagorn J-C.1; Iovanna J.L.1

Source: European Journal of Cell Biology, Volume 80, Number 2, February 2001 , pp. 156-163(8)

Publisher: Urban & Fischer

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Abstract:

Expression of the Cdx1 homeobox gene in epithelial intestinal cells promotes cellular growth and differentiation. Cdx1 and 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 Cdx1-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.

Keywords: Cdx1; PAP I; IEC-6 cells; intestine; cell growth

Language: English

Document Type: Original article

DOI: 10.1078/0171-9335-00148

Affiliations: 1: Laboratoire de Recherche de Physiologie et Pathologie Digestives, INSERM U.315, Marseille/France

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