Cathepsin D in breast cancer.
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, 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 vitro, pro-cathepsin D is an autocrine mitogen on breast cancer cells and can be auto-activated to degrade extracellular matrix and proteoglycans and to activate other proteinases in acidic microenvironments. 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 lymph node-negative tumors. These results suggest that overexpression and possible derouting of cathepsin D plays an important role in invasion and metastasis of breast cancer.
Unité Hormones et Cancer (U 148) INSERM, University of Montpellier, France.
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Rochefort
D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D002402:Cathepsin D / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D002455:Cell Division; D003600:Cytosol / Q000201:enzymology; D004790:Enzyme Induction; D004792:Enzyme Precursors / Q000096:biosynthesis / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009376:Neoplasms, Hormone-Dependent / Q000201:enzymology; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D014407:Tumor Cells, Cultured / Q000201:enzymology
D014408:Biomarkers, Tumor; D004792:Enzyme Precursors; D004967:Estrogens; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C058345:procathepsin D; D002402:Cathepsin D