title: Regulation and role of TGF beta production in breast cancer.
abstract: The influence of antiestrogens on the secretion of transforming growth factor beta (TGF beta) proteins that have an autoinhibitory potential for human cancer cells was studied in the estrogen-responsive human breast cancer cell line, MCF-7: Antiestrogens induce the secretion of TGF beta-1 via a nontranscriptional pathway; TGF beta-1 itself induces TGF beta-2 by a direct transcriptional mechanism; and TGF beta-2 is a marker of antiestrogen action. This hypothesis was confirmed in a clinical study with 18 patients with advanced metastatic breast cancer. TGF beta-2 plasma levels were measured before and after 4 weeks of treatment with tamoxifen. In the majority of patients who responded to the treatment, increasing TGF beta-2 concentrations were seen under therapy. Patients who did not respond did not show changes in the TGF beta-2 plasma level after 4 weeks of treatment. These results suggest that the sequential analysis of TGF beta-1 in plasma before and under treatment with tamoxifen allows the early identification of patients with antiestrogen resistance.
authors.affiliation: Department of Clinical Chemistry, University Hospital Eppendorf, Hamburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Knabbe
authors.forename: A
authors.initials: A
authors.lastname: Kopp
authors.forename: W
authors.initials: W
authors.lastname: Hilgers
authors.forename: D
authors.initials: D
authors.lastname: Lang
authors.forename: V
authors.initials: V
authors.lastname: Müller
authors.forename: G
authors.initials: G
authors.lastname: Zugmaier
authors.forename: W
authors.initials: W
authors.lastname: Jonat
mesh_terms: D001943:Breast Neoplasms / Q000097:blood / Q000378:metabolism*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D006801:Humans; D007536:Isomerism; D012333:RNA, Messenger / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000097:blood / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D004965:Estrogen Antagonists; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D013629:Tamoxifen