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Beta-catenin expression in Dupuytren's disease: potential role for cell–matrix interactions in modulating beta-catenin levels in vivo and in vitro

Oncogene volume 22, pages 3680–3684 (2003)Cite this article

Abstract

Dupuytren's disease (DD) is a superficial fibromatosis of the hand. Although the molecular mechanisms responsible for this disease are unknown, recent studies suggest that beta-catenin may be a key factor involved in fibromatosis. In this study, we analysed the in vivo and in vitro expression levels of beta-catenin in DD, using surgical specimens and primary cell lines. Although no somatic mutations (exon 3) of beta-catenin were detected, Western blot analysis revealed high levels of beta-catenin in diseased palmar fascia, and low to undetectable levels of beta-catenin in patient-matched normal palmar fascia. Immunohistochemistry analysis showed high levels of beta-catenin expression within the disease fascia, as well as cytoplasmic and nuclear accumulations of the protein. Immunoprecipitation of beta-catenin from seven patient lesions showed the protein to be tyrosine phosphorylated. Lastly, Western analysis of three patient-matched (disease and normal fascia) primary cell cultures showed significantly elevated levels of beta-catenin in disease cells cultured in three-dimensional collagen lattices. This is the first extensive in vivo and in vitro characterization of beta-catenin in DD, and the first to suggest that the extracellular matrix may play an important role in modulating beta-catenin stability in DD.

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Acknowledgements

We thank Roy Taylor and Jeanette Botz from the tissue bank (Department of Pathology, London Health Science Centre) for the paraffin sectioning and immunohistochemistry work. This study is supported by grants from the Plastic Surgery Education Fund (BSG, JCH), Canadian Orthopaedic Foundation (JCH, BSG, DCR, JHR, RMM), American Society for Surgery of the Hand (DCR, JCH, RMM, BSG), and the Lawson Health Research Institute's Internal Research Fund (JCH, BSG).

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Authors and Affiliations

  1. Cell and Molecular Biology Laboratory, Hand & Upper Limb Centre, University of Western Ontario, London, Ontario, Canada

    Vincenzo M Varallo, Bing Siang Gan, Shannon Seney, Douglas C Ross, James H Roth, Robert S Richards, Robert M McFarlane & Jeffrey C Howard

  2. Lawson Health Research Institute, University of Western Ontario, London, Ontario, Canada

    Vincenzo M Varallo, Bing Siang Gan, Shannon Seney, Douglas C Ross, James H Roth, Robert S Richards, Robert M McFarlane & Jeffrey C Howard

  3. Department of Surgery, University of Western Ontario, London, Ontario, Canada

    Bing Siang Gan, Douglas C Ross, James H Roth, Robert S Richards, Robert M McFarlane & Jeffrey C Howard

  4. Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada

    Bing Siang Gan

  5. Medical Biophysics, University of Western Ontario, London, Ontario, Canada

    Bing Siang Gan

  6. Biochemistry, University of Western Ontario, London, Ontario, Canada

    Jeffrey C Howard

  7. Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada

    Jeffrey C Howard

  8. Division of Orthopaedic Surgery, Department of Surgery, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada

    Benjamin Alman

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  1. Vincenzo M Varallo
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Correspondence to Jeffrey C Howard.

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Varallo, V., Gan, B., Seney, S. et al. Beta-catenin expression in Dupuytren's disease: potential role for cell–matrix interactions in modulating beta-catenin levels in vivo and in vitro. Oncogene 22, 3680–3684 (2003). https://doi.org/10.1038/sj.onc.1206415

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