Tamoxifen and estrogen effects on TGF-beta formation: role of thrombospondin-1, alphavbeta3, and integrin-associated protein.
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.
Harpel
J G
JG
Department of Cell Biology, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA.
Schultz-Cherry
S
S
Murphy-Ullrich
J E
JE
Rifkin
D B
DB
D000230:Adenocarcinoma / Q000378:metabolism*; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000378:metabolism*; D018955:CD36 Antigens / Q000378:metabolism; D051928:CD47 Antigen; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D053779:Latent TGF-beta Binding Proteins; D012333:RNA, Messenger / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*; D019700:Thrombospondin 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018955:CD36 Antigens; D051928:CD47 Antigen; C497894:CD47 protein, human; D002352:Carrier Proteins; D017077:Culture Media, Conditioned; D004965:Estrogen Antagonists; D004967:Estrogens; D047908:Intracellular Signaling Peptides and Proteins; D053779:Latent TGF-beta Binding Proteins; D012333:RNA, Messenger; D019030:Receptors, Vitronectin; D019700:Thrombospondin 1; D016212:Transforming Growth Factor beta; D013629:Tamoxifen