期刊
GROWTH FACTORS
卷 25, 期 6, 页码 363-372出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/08977190801886905
关键词
insulin-like growth factor II; survivin; resveratrol; MCF-7; breast cancer; mitochondria
资金
- NIGMS NIH HHS [R25 GM060507-01A1, R25 GM060507, R25 GM060507-05, R25 GM060507-02, 2R25GM060507-5] Funding Source: Medline
- NIMHD NIH HHS [5P20 MD001632, P20 MD006988, P20 MD001632-02, P20 MD001632] Funding Source: Medline
Insulin-like growth factor II (IGF-II) plays a pivotal role in fetal and cancer development by signaling through the IGF-I and insulin receptors and activating the estrogen signaling cascade. We previously showed that precursor IGF-II (proIGF-II, the predominant form expressed in cancer) and not mature IGF-II (mIGF-II) blocks resveratrol (RSV) (a phytoalexin/anticancer agent)-induced cell death in MCF-7 cells. We hypothesize that proIGF-II regulates antiapoptotic proteins and/or the mitochondria to inhibit RSV actions and promote cell survival. This study examines the effect of mIGF-II and proIGF-II on survivin expression and mitochondrial polarization in response to RSV RSV inhibits survivin expression and stimulates mitochondrial depolarization, caspase 7 activation and cell death. These effects were completely blocked by the addition of proIGF-II. RSV treatment had no effect on transfected MCF-7 cells constitutively expressing proIGF-II, while IGF-II siRNA transfection decreased survivin levels. Our results provide new insights for the potential use of proIGF-II as target for new anticancer therapies.
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