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Regulation of CD26/DPPIV gene expression by interferons and retinoic acid in tumor B cells

Oncogene volume 19, pages 265–272 (2000)Cite this article

Abstract

Interferons (IFNs α, β and γ) and all trans retinoic acid (RA) have the ability to activate genes with GAS sites. We have found that the promoter of CD26/dipeptidylpeptidase IV (DPPIV) contains a consensus GAS site TTCnnnGAA located at bp-35 to -27, and computer analysis confirmed this sequence to be a putative Stat binding site. Consistent with this finding, we show that IFNs and RA rapidly enhanced CD26 gene and protein expression in chronic B lymphocytic leukemia (B-CLL) cells. Immunoblot analyses revealed that unstimulated B-CLL cells expressed detectable levels of serine/tyrosine-phosphorylated Stat1α, and RA and IFN-γ treatment led to increased levels of tyrosine phosphorylation of Stat1α and its nuclear accumulation. As shown by electrophoretic mobility shift assay, RA and IFN-γ increased the binding of a nuclear protein to the GAS-CD26 element. Shift-Western blotting identified Stat1α as the GAS-CD26 binding factor. Augmented levels of CD26 protein in malignant B cells cultured with IFNs or RA coincided with the enhancement of DPPIV activity. Taken together, our results are in favor of the IFN-/RA-mediated upregulation of CD26/DPPIV in B-CLL through the signaling pathway involving Stat1α and the GAS response element of CD26 promoter.

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Acknowledgements

The authors thank Roussel-Uclaf (Romainville, France) for supplying IFN-γ, Hoffman-La Roche (Basel, Switzerland) for supplying IFN-α2a and retinoic acid, Ares-Serono (Geneva, Switzerland) for supplying IFN-β, and Dr S Scharpé (University of Antwerp, Belgium) for supplying prodipine. We are grateful to Drs I Delic and J Sancéau (Institut Curie, Paris, France) for their invaluable help. We acknowledge Dr JC Francois (Paris, France) for his advice regarding the MatInspector programme. This work was supported by grants from the Institut National de la Santé et de la Recherche Médicale (I.N.S.E.R.M.), the Association pour la Recherche sur le Cancer (A.R.C. no. 1047) and Le Comité des Hauts-de-Seine de La Ligue Nationale Contre le Cancer.

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Authors and Affiliations

  1. Unité 365 INSERM, Institut Curie, Paris, 75231, Cedex 05, France

    Brigitte Bauvois, Mojgan Djavaheri-Mergny & Juana Wietzerbin

  2. Institut Curie, Section de Recherche, Paris, 75231, Cedex 05, France

    Dany Rouillard

  3. Service Hématologie Clinique, Paris, 75231, Cedex 05, France

    Janine Dumont

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Bauvois, B., Djavaheri-Mergny, M., Rouillard, D. et al. Regulation of CD26/DPPIV gene expression by interferons and retinoic acid in tumor B cells. Oncogene 19, 265–272 (2000). https://doi.org/10.1038/sj.onc.1203292

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