Beta-catenin expression in Dupuytren's disease: potential role for cell–matrix interactions in modulating beta-catenin levels in vivo and in vitro
| Autor: | Shannon Seney, Jeffrey C. Howard, Vincenzo M Varallo, Robert M. McFarlane, Benjamin A. Alman, Robert S. Richards, Douglas C. Ross, Bing Siang Gan, James H. Roth |
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| Rok vydání: | 2003 |
| Předmět: |
Cancer Research
Blotting Western Biology Extracellular matrix Western blot In vivo Genetics medicine Humans Phosphorylation Dupuytren's contracture Molecular Biology beta Catenin medicine.diagnostic_test Fascia Anatomy medicine.disease Immunohistochemistry Molecular biology Extracellular Matrix Dupuytren Contracture body regions Blot Cytoskeletal Proteins medicine.anatomical_structure Catenin Mutation Trans-Activators Tyrosine |
| Zdroj: | Oncogene. 22:3680-3684 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1206415 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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