Abstract
We have found that the enhanced activation of latent TGF-beta by human breast carcinoma cell lines either treated with tamoxifen or deprived of estrogen is dependent upon thrombospondin-1 (TSP-1) since activation was blocked by anti-TSP-1 antibodies or by a TSP antagonist peptide. However, TGF-beta formation upon tamoxifen exposure to estrogen withdrawal is associated with decreased levels of soluble TSP-1. A concomitant increase in the expression of the TSP-1 receptors alphavbeta3 and integrin-associated protein (IAP) occurs under these conditions, and antibodies to TSP-1 or to these receptors inhibit increased TGF-beta formation. Therefore, increased cell surface associated TSP-1 enhances latent TGF-beta activation.
Copyright 2001 Academic Press.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenocarcinoma / metabolism*
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Antibodies, Blocking / pharmacology
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Antibodies, Monoclonal / pharmacology
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Antigens, CD / metabolism
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Blotting, Northern
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Breast Neoplasms / metabolism*
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CD36 Antigens / metabolism
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CD47 Antigen
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Carrier Proteins / antagonists & inhibitors
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Carrier Proteins / metabolism
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Culture Media, Conditioned / chemistry
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Culture Media, Conditioned / metabolism
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Electrophoresis, Polyacrylamide Gel
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Estrogen Antagonists / pharmacology
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Estrogens / pharmacology*
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Female
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Humans
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Intracellular Signaling Peptides and Proteins*
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Latent TGF-beta Binding Proteins
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RNA, Messenger / metabolism
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Receptors, Vitronectin / antagonists & inhibitors
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Receptors, Vitronectin / metabolism
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Tamoxifen / pharmacology*
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Thrombospondin 1 / antagonists & inhibitors
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Thrombospondin 1 / metabolism
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Transforming Growth Factor beta / biosynthesis*
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Tumor Cells, Cultured
Substances
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Antibodies, Blocking
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Antibodies, Monoclonal
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Antigens, CD
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CD36 Antigens
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CD47 Antigen
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CD47 protein, human
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Carrier Proteins
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Culture Media, Conditioned
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Estrogen Antagonists
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Estrogens
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Intracellular Signaling Peptides and Proteins
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Latent TGF-beta Binding Proteins
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RNA, Messenger
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Receptors, Vitronectin
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Thrombospondin 1
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Transforming Growth Factor beta
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Tamoxifen