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PMID: 1965795 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Cathepsin D: a protease involved in breast cancer metastasis.

Cancer metastasis reviews ·Vol. 9 ·No. 4 ·1990-12-00 ·Pages 321-31

Rochefort H, Capony F, Garcia M

Abstract

Cathepsin D is an acidic lysosomal protease present in all cells. In estrogen receptor positive and negative breast cancer cell lines, the mRNA coding for pro-cathepsin D is overexpressed and sorting and maturation of the pro-enzyme are altered, via possibly saturation of the Man-6-P/IGF-II receptor, leading to accumulation of the active proteinase in large endosomes and to secretion of the precursor (52K protein). In MCF7 cells, the cathepsin D mRNA is induced directly and transcriptionally by estrogens and indirectly by growth factors. In patients, there is a significant correlation between high cathepsin D concentrations in the cytosol of primary breast cancer and development of metastasis. This marker is independent of other prognostic factors and appears to be particularly useful in axillary node-negative tumors. Transfection of a human cDNA cathepsin D expression vector under the control of SV40 promoter increases the metastatic potential of 3YA1-Ad12 rat tumorigenic cells when intravenously injected into nude mice. The mechanism of cathepsin D-induced metastasis is currently unknown. These results indicate that overexpression of cathepsin D might facilitate breast cancer metastasis, suggesting new possible therapeutic approaches.

MeSH Terms
Breast Neoplasms/enzymology Cathepsin D/metabolism,physiology Enzyme Precursors/metabolism Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic/physiology Humans Mannosephosphates Neoplasm Metastasis/physiopathology Receptor, IGF Type 2 Receptors, Cell Surface/metabolism Tumor Cells, Cultured
Chemicals
Enzyme Precursors Mannosephosphates Receptor, IGF Type 2 Receptors, Cell Surface procathepsin D Cathepsin D
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Rochefort H
Unité Hormones et Cancer (U 148) INSERM, University of Montpellier, France.
Capony F
Garcia M
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44 references, click to expand
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Article Info
Journal
Cancer metastasis reviews
Abbr.
Cancer Metastasis Rev
ISSN
0167-7659
DOI
10.1007/BF00049522
Published
1990-12-00
Pages
321-31
Language
English
Region
Netherlands
NLM ID
8605731
Subset
IM
External Links
PubMed source DOI: 10.1007/BF00049522 View journal details
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