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

被引：0

作者：

Vincenzo M Varallo

Bing Siang Gan

Shannon Seney

Douglas C Ross

James H Roth

Robert S Richards

Robert M McFarlane

Benjamin Alman

Jeffrey C Howard

机构：

[1] Cell and Molecular Biology Laboratory,Department of Surgery

[2] Hand & Upper Limb Centre,Division of Orthopaedic Surgery, Department of Surgery

[3] University of Western Ontario,undefined

[4] Lawson Health Research Institute,undefined

[5] University of Western Ontario,undefined

[6] University of Western Ontario,undefined

[7] Physiology and Pharmacology,undefined

[8] University of Western Ontario,undefined

[9] Medical Biophysics,undefined

[10] University of Western Ontario,undefined

[11] Biochemistry,undefined

[12] University of Western Ontario,undefined

[13] Microbiology and Immunology,undefined

[14] University of Western Ontario,undefined

[15] The Hospital for Sick Children and the University of Toronto,undefined

来源：

Oncogene | 2003年 / 22卷

关键词：

Dupuytren's contracture; fibromatosis; beta-catenin; extracellular matrix;

D O I：

暂无

中图分类号：

学科分类号：

摘要：

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.

引用

页码：3680 / 3684

页数：4