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(American Journal of Pathology. 2003;162:849-860.)
© 2003 American Society for Investigative Pathology

Dystroglycan Expression Is Frequently Reduced in Human Breast and Colon Cancers and Is Associated with Tumor Progression

Alessandro Sgambato*, Mario Migaldi{dagger}, Micaela Montanari*, Andrea Camerini*, Andrea Brancaccio{ddagger}, Giulio Rossi{dagger}, Rodolfo Cangiano*, Carmen Losasso{ddagger}, Giovanni Capelli§, Gian Paolo Trentini{dagger} and Achille Cittadini*

From the Centro di Ricerche Oncologiche "Giovanni XXIII," Istituto di Patologia Generale,* the Istituto di Chimica del Riconoscimento Molecolare,{ddagger} Sezione di Roma (Consiglio Nazionale Ricerche) c/o Istituto di Biochimica e Biochimica Clinica, and the Istituto di Igiene,§ Catholic University, Rome; and the Dipartimento Misto di Anatomia Patologica e di Medicina Legale,{dagger} Sezione di Anatomia Patologica, University of Modena and Reggio Emilia, Modena, Italy

Dystroglycan (DG) is an adhesion molecule responsible for crucial interactions between extracellular matrix and cytoplasmic compartment. It is formed by two subunits, {alpha}-DG (extracellular) and ß-DG (transmembrane), that bind to laminin in the matrix and dystrophin in the cytoskeleton, respectively. In this study we evaluated by Western blot analysis the expression of DG in a series of human cancer cell lines of various histogenetic origin and in a series of human primary colon and breast cancers. Decreased expression of DG was observed in most of the cell lines and in both types of tumors and correlated with higher tumor grade and stage. Analysis of the mRNA levels suggested that expression of DG protein is likely regulated at a posttranscriptional level. Evaluation of {alpha}-DG expression by immunostaining in a series of archival cases of primary breast carcinomas confirmed that {alpha}-DG expression is lost in a significant fraction of tumors (66%). Loss of DG staining correlated with higher tumor stage (P = 0.022), positivity for p53 (P = 0.033), and high proliferation index (P = 0.045). A significant correlation was also observed between loss of {alpha}-DG and overall survival (P = 0.013 by log-rank test) in an univariate analysis. These data indicate that DG expression is frequently lost in human malignancies and suggest that this glycoprotein might play an important role in human tumor development and progression.





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