Document Detail

Down-regulation of laminin-5 in breast carcinoma cells.
MedLine Citation:
PMID:  9848077     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Laminin-5 (ln-5), a large heterotrimeric glycoprotein consisting of an alpha 3, beta 3, and gamma 2 chain, is a component of epithelial cell basement membranes that functions as a ligand of the alpha 3 beta 1 and alpha 6 beta 4 integrins to regulate cell adhesion, migration, and morphogenesis. The ln-5 chains show tissue-specific patterns of regulation in tumors derived from different tissues. For example, ln-5 is often up-regulated in gliomas, gastric carcinomas, and squamous carcinomas and down-regulated in prostate and basal cell carcinomas. Ln-5 expression patterns may represent useful tumor markers and help to elucidate the role of ln-5 in tumor progression in different tissue types. MATERIALS AND METHODS: We have studied ln-5 expression patterns in the breast. mRNA levels were examined in tumor and normal breast epithelial cell lines, tissue samples, and immunomagnetically sorted primary cultures using differential display, Northern blotting, and hybridization arrays. Protein levels were examined by immunoprecipitation. Gene integrity was assessed by Southern blotting of representative cell types. RESULTS: Ln-5 alpha 3, beta 3, and gamma 2 mRNA expression was found to be markedly down-regulated in a panel of breast tumor cell lines when compared with normal breast epithelial cells. Ln-5 mRNA was expressed at relatively high levels in MCF-10A immortal normal breast epithelial cells, long-term cultures of normal breast cells, and sorted primary cultures of normal breast luminal epithelial and myoepithelial cells. Reduced, but detectable, levels of ln-5 tended to be expressed in cell lines derived from early-stage breast tumors, whereas expression was generally not detected in cell lines derived from later-stage tumors. In breast tumor tissue specimens, expression of ln alpha 3 and beta 3 mRNAs tended to be reduced relative to levels observed in adjacent nontumor tissue, whereas in gamma 2 levels were elevated in specimens with increased amounts of myoepithelial cells. These ln-5 expression changes could not be attributed to large-scale mutations or gene rearrangements. Ln-5 protein levels were found to reflect mRNA levels in representative cell lines. At senescence, a growth state believed to suppress tumorigenesis, expression of all three ln-5 mRNAs was up-regulated. CONCLUSION: The down-regulation of ln-5 mRNA expression in breast tumors cells provides a new molecular marker and suggests that ln-5 functions to control tumor progression in the breast.
K J Martin; C P Kwan; K Nagasaki; X Zhang; M J O'Hare; C M Kaelin; R E Burgeson; A B Pardee; R Sager
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular medicine (Cambridge, Mass.)     Volume:  4     ISSN:  1076-1551     ISO Abbreviation:  Mol. Med.     Publication Date:  1998 Sep 
Date Detail:
Created Date:  1999-01-07     Completed Date:  1999-01-07     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  9501023     Medline TA:  Mol Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  602-13     Citation Subset:  IM    
Division of Cancer Genetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
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MeSH Terms
Breast / cytology,  metabolism*
Breast Neoplasms / genetics,  metabolism*,  pathology
Cell Adhesion Molecules / biosynthesis,  chemistry,  genetics*
Cells, Cultured
Epithelial Cells / cytology,  metabolism,  pathology
Gene Expression Regulation
Gene Expression Regulation, Neoplastic*
RNA, Messenger / analysis
Reference Values
Transcription, Genetic*
Tumor Cells, Cultured
Reg. No./Substance:
0/Cell Adhesion Molecules; 0/RNA, Messenger; 0/kalinin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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