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Resveratrol regulates insulin-like growth factor-II in breast cancer cells
Sharda Vyas1, Yayesh Asmerom, Daisy D De León
1Department of Anatomy, CSP 11012, Loma Linda University, Loma Linda, California 92350, USA.
Abstract:
IGF-II is a potent mitogen and inhibitor of apoptosis in breast cancer. Regulation of IGF-II is complex and includes inhibition by tumor suppressors, stimulation by oncogenes, and imprinting and hormonal regulation by estrogens. Resveratrol (RSV) is a phytoestrogen that displays estrogen-like agonistic and antagonistic activity. Recent studies have shown that RSV inhibits the growth of breast cancer cells and may represent a potent agent in chemopreventive therapy. Because 17beta-estradiol regulates IGF-II, we hypothesized that RSV may have a similar effect on IGF-II. The present study was designed to examine whether: 1) RSV modulates IGF-II in breast cancer cells; 2) regulation of IGF-II by RSV is dependent on the ER status; and 3) IGF-II (not IGF-I) mediates RSV effects on breast cancer cells. Treatment of MCF-7 and T47D cells with RSV (10(-6) M) caused stimulation of precursor IGF-II mRNA and protein; this effect was blocked by coincubation with 17beta-estradiol (10(-9) M). Cell growth stimulated by RSV (10(-6) M) was blocked by addition of a blocking IGF-I receptor antibody, or the antiestrogen tamoxifen (10(-7) M). In contrast, RSV treatment (10(-4) M) inhibited IGF-II secretion and cell growth in MCF-7 and T47D cells. No increase in IGF-II levels is seen in estrogen receptor (-) MCF-10 cells, even though cell growth was inhibited by RSV 10(-4) M and precursor IGF-II blocked the inhibitory effect of resveratrol. No change in IGF-I was observed with RSV treatment (10(-6) to 10(-4) M). Our study demonstrates that RSV regulates IGF-II and that IGF-II mediates RSV effect on cell survival and growth in breast cancer cells.
Insights
Resveratrol (RSV) affects Insulin-like Growth Factor-II (IGF-II) in breast cancer cells. This study shows IGF-II mediates RSV
Area of Science:
- Endocrinology
- Molecular Biology
- Cancer Research
Background:
- Insulin-like Growth Factor-II (IGF-II) is a key regulator in breast cancer, influencing cell proliferation and apoptosis.
- Resveratrol (RSV), a phytoestrogen, exhibits anti-cancer properties and interacts with estrogen pathways.
- Estrogen's role in regulating IGF-II suggests a potential link between RSV and IGF-II in breast cancer.
Purpose of the Study:
- To investigate if RSV modulates IGF-II expression and secretion in breast cancer cells.
- To determine if RSV's effect on IGF-II is dependent on estrogen receptor (ER) status.
- To ascertain whether IGF-II mediates the effects of RSV on breast cancer cell growth and survival.
Main Methods:
- Treatment of ER-positive (MCF-7, T47D) and ER-negative (MCF-10) breast cancer cells with varying concentrations of RSV.
- Analysis of precursor IGF-II mRNA and protein levels.
- Assessment of cell growth inhibition and survival using IGF-I receptor blocking antibodies and tamoxifen.
- Evaluation of IGF-I levels.
Main Results:
- Low-dose RSV (10^-6 M) stimulated IGF-II in ER-positive cells, an effect blocked by 17beta-estradiol.
- RSV-stimulated growth was inhibited by an IGF-I receptor antibody or tamoxifen.
- High-dose RSV (10^-4 M) inhibited IGF-II secretion and cell growth in ER-positive cells.
- RSV inhibited cell growth in ER-negative cells, but IGF-II levels did not increase.
Conclusions:
- Resveratrol differentially regulates IGF-II in breast cancer cells, with effects dependent on concentration and ER status.
- IGF-II plays a mediating role in both the growth-promoting and growth-inhibitory effects of RSV on breast cancer cells.
- These findings highlight a complex interaction between RSV, IGF-II, and ER signaling in breast cancer therapy and chemoprevention.
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