Beta-catenin expression in Dupuytren's disease: potential role for cell-matrix interactions in modulating beta-catenin levels in vivo and in vitro.
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.
Varallo
Vincenzo M
VM
Cell and Molecular Biology Laboratory, Hand & Upper Limb Centre, University of Western Ontario, London, Canada.
Gan
Bing Siang
BS
Seney
Shannon
S
Ross
Douglas C
DC
Roth
James H
JH
Richards
Robert S
RS
McFarlane
Robert M
RM
Alman
Benjamin
B
Howard
Jeffrey C
JC
D015153:Blotting, Western; D003598:Cytoskeletal Proteins / Q000032:analysis*; D004387:Dupuytren Contracture / Q000378:metabolism*; D005109:Extracellular Matrix / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D010766:Phosphorylation; D015534:Trans-Activators / Q000032:analysis*; D014443:Tyrosine; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin; D014443:Tyrosine