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Induction of the adenoma-carcinoma progression and Cdc25A-B phosphatases by the trefoil factor TFF1 in human colon epithelial cells

Oncogene volume 25, pages 6628–6636 (2006)Cite this article

Abstract

TFF1 is overexpressed in inflammatory diseases and human cancers of the digestive and urogenital systems. To examine the transforming potential of TFF1 in human colon epithelial cells, premalignant PC/AA/C1 adenoma cells (PC) derived from a patient with familial adenomatous polyposis (FAP) were transformed by the TFF1 cDNA and used as a model of the adenoma–carcinoma transition. Constitutive expression of TFF1 increased anchorage-independent cell growth in soft agar, and induced or potentiated the growth of colon PC-TFF1 and kidney MDCKts.src-TFF1 tumor xenografts in athymic mice. This resulted in reduction of thapsigargin-induced apoptosis and promotion of collagen type I invasion through several oncogenic pathways. Using the differential display approach to identify TFF1 target genes, we found that the dual specific phosphatases Cdc25A and B implicated in cell cycle transitions are strongly upregulated under active forms in both PC-TFF1 and HCT8/S11-TFF1 colon cancer cells. Accordingly, TFF1 expression is absent in normal human colon crypts but is induced in correlation with Cdc25a and b transcript levels and tumor grade in familial and sporadic colon adenomas and carcinomas. We propose that TFF1 and Cdc25A-B cooperate with other dominant oncogenic pathways to induce the adenoma and adenocarcinoma transitions. Agents that target TFF1/Cdc25 signaling pathways may be useful for treating patients with TFF1-positive solid tumors.

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Acknowledgements

This work was supported by INSERM, the French association against cancer (ARC), and FWO-Vlaanderen and FORTIS-Verzekeringen (Brussels, Belgium).

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Author notes

  1. S Attoub

    Present address: Faculty of Medicine and Health Sciences, P.O. Box: 17666, Al Ain, United Arab Emirates

  2. S Rodrigues and C M Rodrigue: These authors contributed equally to this work.

Authors and Affiliations

  1. INSERM U. 673 and University of Paris VI, Molecular and Clinical Oncology of Solid tumors, Paris, Cedex 12, France

    S Rodrigues, C M Rodrigue, S Attoub, S Emami & C Gespach

  2. Department of Pathology, Hôpital Saint-Antoine, Paris, Cedex 12, France

    J F Fléjou & C Gespach

  3. The Laboratory of Experimental Cancerology, Ghent University Hospital, Ghent, Belgium

    E Bruyneel & M Bracke

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  1. S Rodrigues
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Correspondence to C Gespach.

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Rodrigues, S., Rodrigue, C., Attoub, S. et al. Induction of the adenoma-carcinoma progression and Cdc25A-B phosphatases by the trefoil factor TFF1 in human colon epithelial cells. Oncogene 25, 6628–6636 (2006). https://doi.org/10.1038/sj.onc.1209665

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