Journal
GROWTH FACTORS
Volume 29, Issue 2-3, Pages 82-93Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/08977194.2011.565003
Keywords
IGF-2; estrogen receptors; IGF-1R; IR; breast cancer
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Funding
- [5P20MD001632]
- [NIGMS 5R25GM060507]
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The estrogen receptor (ER) is a primary target for breast cancer (BC) treatment. As BC progresses to estrogen-independent growth, the insulin-like growth factor-1 receptor (IGF-1R) and the ER interact in synergistic cross-talk mechanisms, which result in enhanced activation of both receptors' signaling cascades. Insulin-like growth factor-2 (IGF-2) is critical in BC progression and its actions are mediated by the IGF-1R. Our previous studies showed that IGF-2 regulates survival genes that protect the mitochondria and promote chemoresistance. In this study, we analyzed BC cells by subcellular fractionation, Western-Blot, qRT-PCR, and siRNA analysis. Our results demonstrate that IGF-2 activates ER-alpha alpha and ER-beta beta, and modulates their translocation to the nucleus, membrane organelles, and the mitochondria. IGF-2 actions are mediated by the IGF-1R and the insulin receptor. This novel mechanism of IGF-2 synergistic cross-talk signaling with ER-alpha alpha and ER-beta beta can promote estrogen-independent BC progression and provide new therapeutic targets for the treatment of BC patients.
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