Journal ArticleDOI
Cathepsin D: a protease involved in breast cancer metastasis
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TLDR
The results indicate that overexpression of cathepsin D might facilitate breast cancer metastasis, suggesting new possible therapeutic approaches.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.read more
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References
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Journal ArticleDOI
Lysosomal Enzymes and their Receptors
K von Figura,Andrej Hasilik +1 more
TL;DR: The Golgi is an ideal environment for the synthesis and modification of 6-Phosphate Residues and the role of these modifications in the development of LYSOSOMAL ENZYMES is under investigation.
Journal ArticleDOI
Insulin-like growth factor II receptor as a multifunctional binding protein.
David O. Morgan,David O. Morgan,Jeffrey C. Edman,David Standring,Victor A. Fried,Michele C. Smith,Richard A. Roth,William J. Rutter +7 more
TL;DR: The primary structure of human insulin-like growth factor II receptor, predicted from the complementary DNA sequence, reveals a transmembrane receptor molecule with a large extracellular domain made up of fifteen repeat sequences and a small region homologous to the collagen-binding domain of fibronectin.
Journal ArticleDOI
A secreted glycoprotein induced by estrogen in human breast cancer cell lines
Bruce Westley,Henri Rochefort +1 more
TL;DR: The 46K protein, which accounts for 40% of 35S-methionine incorporation into secreted proteins, is only induced by steroids able to interact with the estrogen receptor, and makes these cell lines excellent in vitro systems for studying the mechanism of estrogen and anti-estrogen action.
Journal ArticleDOI
Cathepsin D and prognosis in breast cancer.
TL;DR: It is concluded that cathepsin D may be an independent predictor of early recurrence and death in node-negative breast cancer.
Journal ArticleDOI
Lysosomal cathepsin B: correlation with metastatic potential.
TL;DR: The activity of the lysosomal proteinase cathepsin B is significantly elevated in a variant of the B16 melanoma with high metastatic potential.