Differential regulation of insulin-like growth factor-binding protein-3 protease activity in MCF-7 breast cancer cells by estrogen and transforming growth factor-beta1.
We have examined the regulation of an insulin-like growth factor-binding protein-3 (IGFBP-3) protease secreted by MCF-7 human breast cancer cells using a ligand-binding assay that relies on the decrease in affinity for des(1-3)IGF-I that occurs when IGFBP-3 becomes proteolyzed. IGFBP-3 protease activity was not altered by treatment of MCF-7 cells with all-trans-retinoic acid, vitamin D, epidermal growth factor, platelet-derived growth factor, insulin, or forskolin. However, estradiol was a potent stimulator of IGFBP-3 protease activity, with a significant and maximal effect at 1 nM. This was prevented by cotreatment with tamoxifen, which had no significant effect in the absence of estradiol. By contrast, TGFbeta1 dose dependently inhibited the amount of protease activity secreted by MCF-7 cells, with complete reversal of IGFBP-3 degradation apparent in response to 10 ng/ml TGFbeta1. This study has demonstrated that estrogens and TGFbeta1, factors that are stimulatory and inhibitory, respectively, for MCF-7 cell growth, also stimulate and inhibit the production of an enzyme capable of proteolyzing the growth inhibitory protein IGFBP-3.
Salahifar
H
H
Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales, Australia.
Baxter
R C
RC
Martin
J L
JL
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology*; D017077:Culture Media, Conditioned; D004591:Electrophoresis, Polyacrylamide Gel; D010450:Endopeptidases / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D004965:Estrogen Antagonists; D004967:Estrogens; D008024:Ligands; D016212:Transforming Growth Factor beta; D004958:Estradiol; D010450:Endopeptidases; C080473:insulin-like growth factor binding protein-3 protease