Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-3-6
pubmed:abstractText
Abnormalities in the interactions of cells with the extracellular matrix (ECM) play an important role in the development and progression of many types of cancer and are a hallmark of malignant transformation. The dystroglycan (DG) complex is a transmembrane glycoprotein that forms a continuous link from the ECM to the actin cytoskeleton, providing structural integrity and perhaps transducing signal, in a manner similar to integrins. Deregulated expression of DG has been reported in a variety of human malignancies and related to tumor differentiation and aggressiveness. In breast cancer, reduced DG expression has been associated with patient survival and with loss of differentiation of tumor cells. Limited data are available on DG physiology in epithelial cells. In this study, we used the HC11 spontaneously immortalized murine mammary epithelial cells to study DG function(s) and regulation in normal cells. We found that expression of DG protein and mRNA is cell-cycle and cell-density regulated in these cells. Moreover, expression of both DG subunits increased upon lactogenic differentiation of the HC11 cells. The turnover of cell-surface-expressed DG was evaluated in the same cells and half-life of DG subunits was evaluated to be about 12 h. DG-specific small inhibitory RNAs were used to analyze the effects of a reduced expression of DG in these cells. Cells in which DG expression was suppressed were growth inhibited, accumulated in the S-phase of the cell cycle, failed to undergo lactogenic differentiation, and displayed an increase in the percentage of apoptotic cells. Moreover, changes were observed in the expression and/or activity of several molecules involved in cell growth control. These results demonstrate that DG expression is tightly regulated in normal mammary epithelial cells and support the hypothesis that DG is involved in several functions other than structural integrity in these cells. This finding provides new insight into the roles played by DG in epithelial cell physiology and will contribute to our understanding of its involvement in the process of epithelial cell transformation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9541
pubmed:author
pubmed:issnType
Print
pubmed:volume
207
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
520-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16447256-Animals, pubmed-meshheading:16447256-Apoptosis, pubmed-meshheading:16447256-Cell Cycle, pubmed-meshheading:16447256-Cell Differentiation, pubmed-meshheading:16447256-Cell Line, Transformed, pubmed-meshheading:16447256-Cell Proliferation, pubmed-meshheading:16447256-Dystroglycans, pubmed-meshheading:16447256-Epithelial Cells, pubmed-meshheading:16447256-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:16447256-Female, pubmed-meshheading:16447256-Gene Expression, pubmed-meshheading:16447256-Mammary Glands, Animal, pubmed-meshheading:16447256-Mammary Neoplasms, Animal, pubmed-meshheading:16447256-Mice, pubmed-meshheading:16447256-Mice, Inbred BALB C, pubmed-meshheading:16447256-PTEN Phosphohydrolase, pubmed-meshheading:16447256-Phosphorylation, pubmed-meshheading:16447256-Prolactin, pubmed-meshheading:16447256-Proto-Oncogene Proteins c-akt, pubmed-meshheading:16447256-RNA, Small Interfering
pubmed:year
2006
pubmed:articleTitle
Analysis of dystroglycan regulation and functions in mouse mammary epithelial cells and implications for mammary tumorigenesis.
pubmed:affiliation
Centro di Ricerche Oncologiche "Giovanni XXIII", Istituto di Patologia Generale, Catholic University, Rome, Italy. asgambato@rm.unicatt.it
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't