Document Detail


Cystatin m: a novel candidate tumor suppressor gene for breast cancer.
MedLine Citation:
PMID:  15466187     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The contribution of pericellular proteolysis to tumor progression is well documented. To better understand protease biology and facilitate clinical translation, specific proteolytic systems need to be better defined. In particular, the precise role of endogenous protease inhibitors still needs to be deciphered. We reported previously that cystatin M, a potent endogenous inhibitor of lysosomal cysteine proteases, significantly suppressed in vitro cell proliferation, migration, and Matrigel invasion. Here, we show that scid mice orthotopically implanted with breast cancer cells expressing cystatin M show significantly delayed primary tumor growth and lower metastatic burden in the lungs and liver when compared with mice implanted with mock controls. The incidence of metastasis, however, appeared to be unaltered between the cystatin M group and the control group. Experimental metastasis assays suggest that cystatin M suppressed tumor cell proliferation at the secondary site. By using laser capture microdissection and quantitative reverse transcription-polymerase chain reaction, we found consistent expression of cystatin M in normal human breast epithelial cells, whereas expression was decreased by 86% in invasive ductal carcinoma (IDC) cells of stage I to IV patients. Complete loss of expression of cystatin M was observed in two of three IDCs from stage IV patients. Immunohistochemical studies confirmed that expression of cystatin M in IDCs was partially or completely lost. We propose cystatin M as a novel candidate tumor suppressor gene for breast cancer.
Authors:
Jun Zhang; Ravi Shridhar; Qun Dai; Jin Song; Shayne C Barlow; Lijia Yin; Bonnie F Sloane; Fred R Miller; Carol Meschonat; Benjamin D L Li; Fleurette Abreo; Daniel Keppler
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer research     Volume:  64     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-10-06     Completed Date:  2004-11-16     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6957-64     Citation Subset:  IM    
Affiliation:
Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130-3932, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Breast Neoplasms / genetics*,  metabolism,  pathology
Cell Division / physiology
Cell Line, Tumor
Cystatin M
Cystatins / biosynthesis,  genetics*
Female
Genes, Tumor Suppressor*
Humans
Immunohistochemistry
Liver Neoplasms, Experimental / pathology,  secondary
Lung Neoplasms / pathology,  secondary
Mice
Mice, Inbred ICR
Mice, SCID
Neoplasm Staging
Transfection
Grant Support
ID/Acronym/Agency:
CA36481/CA/NCI NIH HHS; CA91785/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/CST6 protein, human; 0/Cystatin M; 0/Cystatins

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