Volume 127, Issue 9 pp. 2051-2062
Cancer Cell Biology

Intraepithelial p63-dependent expression of distinct components of cell adhesion complexes in normal esophageal mucosa and squamous cell carcinoma

Amélie Thépot

Corresponding Author

Amélie Thépot

Molecular Carcinogenesis Group and Epigenetics Group, IARC, Lyon, France

Banque de Tissus et cellules, Hôpital E. Herriot, Lyon, France

Tel.: 33-4-72-73-84-62, Fax: 33-4-72-73-83-22

Group of Molecular Carcinogenesis and Biomarkers, IARC, 150 cours Albert Thomas, 69372 Lyon Cedex 08, FranceSearch for more papers by this author
Agnès Hautefeuille

Agnès Hautefeuille

Molecular Carcinogenesis Group and Epigenetics Group, IARC, Lyon, France

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Marie-Pierre Cros

Marie-Pierre Cros

Molecular Carcinogenesis Group and Epigenetics Group, IARC, Lyon, France

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Behnoush Abedi-Ardekani

Behnoush Abedi-Ardekani

Molecular Carcinogenesis Group and Epigenetics Group, IARC, Lyon, France

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Aurélia Pétré

Aurélia Pétré

Molecular Carcinogenesis Group and Epigenetics Group, IARC, Lyon, France

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Odile Damour

Odile Damour

Banque de Tissus et cellules, Hôpital E. Herriot, Lyon, France

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Vladimir Krutovskikh

Vladimir Krutovskikh

Molecular Carcinogenesis Group and Epigenetics Group, IARC, Lyon, France

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Pierre Hainaut

Corresponding Author

Pierre Hainaut

Molecular Carcinogenesis Group and Epigenetics Group, IARC, Lyon, France

Tel.: 33-4-72-73-84-62, Fax: 33-4-72-73-83-22

Group of Molecular Carcinogenesis and Biomarkers, IARC, 150 cours Albert Thomas, 69372 Lyon Cedex 08, FranceSearch for more papers by this author
First published: 26 August 2010
Citations: 18

Abstract

TP63 gene is a member of TP53 tumor suppressor gene family that encodes several protein isoforms involved in the process of epithelial stratification and in epithelial-mesenchyme interactions. TP63 is amplified in a significant proportion of squamous cell carcinoma of the esophagus (ESCC), resulting in the hyper-expression of ΔNp63 as the major p63 isoform. To better understand the contribution of this high expression to tumorigenesis, we have analyzed the impact of intraepithelial p63 expression on the expression of cell adhesion complexes in normal esophagus and in ESCC cell lines. Cells expressing p63 showed an adhesion pattern characterized by lack of tight junctions and presence of adherens junctions. Cell differentiation was accompanied by a decrease in p63 and by a shift to adhesion patterns involving tight junctions. Silencing of p63 mRNA in ESCC cell lines resulted in a similar shift, characterized by increased expression of component of tight junctions, decreased cell-to-cell communication and downregulation of cell proliferation. These results indicate that ΔNp63 may contribute to esophageal squamous carcinogenesis by maintaining cell adhesion patterns compatible with cell proliferation.

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