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Insulin-like growth factor binding protein 3 (IGF-BP3) inhibits estrogen-stimulated breast cancer cell proliferation
1Lady Davis Institute, McGill University, Montreal, Quebec, Canada.
Abstract:
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.
Insights
Insulin-like growth factor-binding protein 3 (IGF-BP3) inhibits MCF7 cell proliferation. This IGF-BP3 demonstrates antagonism against steroid-stimulated growth, supporting its role in antiestrogen therapy.
Area of Science:
- Endocrinology
- Cell Biology
- Cancer Research
Background:
- Antiestrogen therapy in breast cancer can lead to increased IGF-BP3 in cell media.
- This accumulation correlates with reduced responsiveness to IGFs.
Purpose of the Study:
- To investigate the direct effect of IGF-BP3 on MCF7 cell proliferation.
- To determine if IGF-BP3 antagonizes estrogen-stimulated growth.
Main Methods:
- MCF7 cells were cultured in steroid-stripped, serum-containing media.
- Recombinant human IGF-BP3 (rhIGF-BP3) was added to assess its effect on proliferation.
- [3H]thymidine incorporation was used to measure proliferation rates.
Main Results:
- rhIGF-BP3 significantly attenuated serum-stimulated MCF7 cell proliferation, with maximal inhibition of 40% at 6.25nM.
- Estradiol (E2) significantly stimulated MCF7 proliferation.
- Co-incubation with 50nM IGF-BP3 significantly attenuated E2-stimulated proliferation.
Conclusions:
- IGF-BP3 directly inhibits MCF7 cell proliferation.
- IGF-BP3 antagonizes steroid-stimulated proliferation.
- These findings support the hypothesis that antiestrogen-induced IGF-BP3 accumulation contributes to cytostatic effects.