Insulin-like growth factor binding protein 3 (IGF-BP3) inhibits estrogen-stimulated breast cancer cell proliferation.
We have recently demonstrated that exposure of MCF7 cells to antiestrogens in vitro results in both accumulation of IGF-BP3 in media and reduced mitogenic responsivity to IGFs (Cancer Res. 53:5193-5198). We show here that MCF7 cell proliferation in steroid-stripped, serum containing media is significantly attenuated by rhIGF-BP3 (p < 0.05), with a maximal 40% inhibition of serum stimulated growth achieved by 6.25nM IGF-BP3. 10(-10) M estradiol (E2) significantly stimulated MCF7 proliferation, and co-incubation of estrogen containing cultures with 50nM IGF-BP3 resulted in significant attenuation of the estrogen-stimulated proliferation ([3H]thymidine incorporation: E2, 147 +/- 18% of control; E2 +/- IGF-BP3, 111 +/- 18% of control, p < 0.05). These results demonstrate antagonism of steroid stimulated proliferation by an IGF binding protein and are compatible with the hypothesis that antiestrogen-induced accumulation of IGF-BP3 in the conditioned media of MCF7 cells contributes to the cytostatic action of these drugs.
Pratt
S E
SE
Lady Davis Institute, McGill University, Montreal, Quebec, Canada.
Pollak
M N
MN
D001943:Breast Neoplasms; D002352:Carrier Proteins / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins; D007700:Kinetics; D011994:Recombinant Proteins; D013002:Somatomedins / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D004273:DNA, Neoplasm; D018969:Insulin-Like Growth Factor Binding Proteins; D011994:Recombinant Proteins; D013002:Somatomedins; D004958:Estradiol; D013936:Thymidine