Dystroglycan expression is frequently reduced in human breast and colon cancers and is associated with tumor progression.
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 beta-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.
Sgambato
Alessandro
A
Centro di Ricerche Oncologiche Giovanni XXIII, Istituto di Patologia Generale, Catholic University, Rome, Italy. asgambato@rm.unicatt.it
Migaldi
Mario
M
Montanari
Micaela
M
Camerini
Andrea
A
Brancaccio
Andrea
A
Rossi
Giulio
G
Cangiano
Rodolfo
R
Losasso
Carmen
C
Capelli
Giovanni
G
Trentini
Gian Paolo
GP
Cittadini
Achille
A
D000368:Aged; D000704:Analysis of Variance; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D049030:Dystroglycans; D016189:Dystrophin / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D016189:Dystrophin; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D049030:Dystroglycans