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TP63 P2 promoter functional analysis identifies β-catenin as a key regulator of ΔNp63 expression

Oncogene volume 30, pages 4656–4665 (2011)Cite this article

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Abstract

The ΔNp63 protein, a product of the TP63 gene that lacks the N-terminal domain, has a critical role in the maintenance of self renewal and progenitor capacity in several types of epithelial tissues. ΔNp63 is frequently overexpressed in squamous cell carcinoma (SCC) and in some other epithelial tumours. This overexpression may contribute to tumour progression through dominant-negative effects on the transcriptionally active (TA) isoforms of the p53 family (TAp63, TAp73 and p53), as well as through independent mechanisms. However, the molecular basis of ΔNp63 overexpression is not fully understood. Here, we show that the expression of ΔNp63 is regulated by the Wnt/β-catenin pathway in human hepatocellular carcinoma (HCC) and SCC cell lines. This regulation operates in particular through TCF/LEF sites present in the P2 promoter of TP63. In addition, we show that ΔNp63 and β-catenin are frequently coexpressed and accumulated in oesophageal SCC, but not in HCC. These results suggest that activation of the β-catenin pathway may contribute to overexpression of ΔNp63 during tumour progression, in a cell type-specific manner.

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Abbreviations

CBF:

CAAT-binding factor

HCC:

hepatocellular carcinoma

PBS:

Pitx2-binding site

RE:

responsive element

SCC:

squamous cell carcinoma

TA:

transcriptionally active

TBE:

TCF/LEF-binding element; UTR, untranslated region

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Acknowledgements

We thank Drs W Dinjens (University Medical Center, Rotterdam, The Netherlands) and A Costanzo (University of Rome, Italy) for the generous gift of TE-10 cells and pGL3-P2 plasmid, respectively; Drs J Zucmann-Rossi (INSERM U674, Paris, France) and B Terris (Institut Cochin, Paris, France) for the analysis of ΔNp63 expression in HCC samples; Dr B Abedi for her help for IHC experiments; Dr G Martel-Planche and A Masquelet and Ms A Durand and A Charnay for technical assistance; Drs S Sentis, G Hinkal and S and D Cox for critical reading of the manuscript. This project was supported by INSERM and the Association pour la Recherche contre le Cancer (grant number 3117). CR and HS were funded by the French Ligue Nationale Contre le Cancer, AP by the French Ministère de l’Enseignement et de la Recherche, and ET, PT, and VT by the International Agency for Research on Cancer.

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Author notes

  1. C Ruptier & I Lafosse

    Present address: Current address: Genoway, 181 avenue Jean Jaurès, 69007 Lyon, France.,

  2. A Granjon

    Present address: Current address: CNRS UMR5123 Physiologie Intégrative Cellulaire et Moléculaire, 43 bd du 11 novembre 1918, 69622 Villeurbanne Cedex, France.,

  3. P Tanière

    Present address: Current address: Department of Cellular Pathology, The Medical School, University of Birmingham, Edgbaston, Birmingham B115 2TT, UK.,

  4. H Shi

    Present address: Current address: Knobelstrasse 3, 5611 Anglikon, Switzerland.,

  5. A Petitjean

    Present address: Current address: Résidence Roche Arnaud, 27 rue Emile Reynaud, 43000 Le Puy en Velay, France.,

  6. E Taranchon-Clermont

    Present address: Current address: CEPH, 27 rue Juliette Dodu, 75010 Paris, France.,

  7. V Tribollet

    Present address: Current address: CNRS UMR5242- IGFL, ENS Lyon, 46 allée d’Italie, 69364 Lyon cedex 07, France.,

  8. C Ruptier and A De Gaspéris: These authors contributed equally to this work.

Authors and Affiliations

  1. Université de Lyon, Lyon, France

    C Ruptier, A De Gaspéris, S Ansieau, A Granjon, I Lafosse, V Tribollet, T Voeltzel, J-Y Scoazec, V Maguer-Satta, A Puisieux & C Caron de Fromentel

  2. INSERM U1052, Centre de Recherche en Cancérologie de Lyon, Lyon, France

    C Ruptier, A De Gaspéris, S Ansieau, A Granjon, I Lafosse, V Tribollet, T Voeltzel, J-Y Scoazec, V Maguer-Satta, A Puisieux & C Caron de Fromentel

  3. CNRS5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France

    C Ruptier, A De Gaspéris, S Ansieau, A Granjon, I Lafosse, V Tribollet, T Voeltzel, J-Y Scoazec, V Maguer-Satta, A Puisieux & C Caron de Fromentel

  4. International Agency for Research on Cancer, Lyon, France

    P Tanière, H Shi, A Petitjean, E Taranchon-Clermont & P Hainaut

  5. Hospices Civils de Lyon, Hôpital E. Herriot, Service central d’Anatomie et de Cytologie Pathologiques, Lyon, France

    J-Y Scoazec

  6. Centre Léon Bérard, Lyon, France

    A Puisieux

  7. Institut Universitaire de France, Paris, France

    A Puisieux

  8. Département Endocrinologie Métabolisme et Cancer, Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France

    C Cavard

  9. INSERM U567, Paris, France

    C Cavard

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  1. C Ruptier
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Correspondence to C Caron de Fromentel.

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Ruptier, C., De Gaspéris, A., Ansieau, S. et al. TP63 P2 promoter functional analysis identifies β-catenin as a key regulator of ΔNp63 expression. Oncogene 30, 4656–4665 (2011). https://doi.org/10.1038/onc.2011.171

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