Document Detail


Missense polymorphism (C/T224) in the human cathepsin D pro-fragment determined by polymerase chain reaction--single strand conformational polymorphism analysis and possible consequences in cancer cells.
MedLine Citation:
PMID:  8204364     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Overexpression of cathepsin D in human breast cancers is associated with a higher risk of relapse and metastasis. Also, pro-enzyme routing is altered in several tumoral mammary cell lines, leading to its hypersecretion. MCF7 cells compared to normal kidney carry a C-->T transition at position 224 in the cathepsin D gene which converts Ala to valine in its pro-fragment. Using polymerase chain reaction-single strand conformational polymorphism analysis (PCR-SSCP), the variant T allele frequency was found to be 23-30%, and equally distributed in cancer and normal cells. Six to nine per cent of genotypes were homozygous T/T, 34-41% were heterozygous T/C and 50-59% were homozygous C/C. Moreover, genotypes were identical in 19 out of 20 matched sets of tumoral mammary cells and normal white blood cells from the same patients. Loss of heterozygosity was noted in 1 case. C/T224 transition is thus not due to a somatic event. However, this missense polymorphism might modify procathepsin D secretion and/or maturation in breast cancer cells.
Authors:
I Touitou; F Capony; J P Brouillet; H Rochefort
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of cancer (Oxford, England : 1990)     Volume:  30A     ISSN:  0959-8049     ISO Abbreviation:  Eur. J. Cancer     Publication Date:  1994  
Date Detail:
Created Date:  1994-07-13     Completed Date:  1994-07-13     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9005373     Medline TA:  Eur J Cancer     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  390-4     Citation Subset:  IM    
Affiliation:
Unité Hormones et Cancer (U148) INSERM, University of Montpellier 1, Department of Cell Biology, France.
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MeSH Terms
Descriptor/Qualifier:
Alleles
Base Sequence
Breast Neoplasms / enzymology,  genetics*
Cathepsin D / biosynthesis,  genetics*
Female
Gene Frequency
Humans
Molecular Sequence Data
Mutation
Polymerase Chain Reaction
Polymorphism, Genetic / genetics*
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
EC 3.4.23.5/Cathepsin D

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


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