Cathepsin D: a protease involved in breast cancer metastasis.
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.
Rochefort
H
H
Unité Hormones et Cancer (U 148) INSERM, University of Montpellier, France.
Capony
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F
Garcia
M
M
D001943:Breast Neoplasms / Q000201:enzymology*; D002402:Cathepsin D / Q000378:metabolism / Q000502:physiology*; D004792:Enzyme Precursors / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D008360:Mannosephosphates; D009362:Neoplasm Metastasis / Q000503:physiopathology; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004792:Enzyme Precursors; D008360:Mannosephosphates; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface; C058345:procathepsin D; D002402:Cathepsin D