Regulation and role of TGF beta production in breast cancer.
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.
Knabbe
C
C
Department of Clinical Chemistry, University Hospital Eppendorf, Hamburg, Germany.
Kopp
A
A
Hilgers
W
W
Lang
D
D
Müller
V
V
Zugmaier
G
G
Jonat
W
W
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
D004965:Estrogen Antagonists; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D013629:Tamoxifen