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Insulin-like growth factor-II regulates PTEN expression in the mammary gland

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Title: Insulin-like growth factor-II regulates PTEN expression in the mammary gland
Author: Moorehead, R. A.; Hojilla, C. V.; De Belle, I.; Wood, G. A.; Fata, J. E.; Adamson, E. D.; Watson, K. L.; Edwards, D. R.; Khokha, R.
Abstract: The tumor suppressor PTEN is altered in many cancers, including breast cancer, but only a handful of factors are known to control its expression. PTEN plays a vital role in cell survival and proliferation by regulating Akt phosphorylation, a key component of the phosphatidylinositol 3 kinase (PI3K) pathway. Here we show that insulin-like growth factor-II (IGF-II), which signals through PI3K, regulates PTEN expression in the mammary gland. IGF-II injection into mouse mammary gland significantly increased PTEN expression. Transgenic IGF-II expression also increased mammary PTEN protein, leading to reductions in Akt phosphorylation, epithelial proliferation, and mammary morphogenesis. IGF-II induced PTEN promoter activity and protein levels and this involved the immediate early gene egr-1. Thus, we have identified a novel negative feedback loop within the PI3K pathway where IGF-II induces PTEN expression to modulate its physiologic effects.
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Publisher: American Society for Biochemistry and Molecular Biology
URI: http://hdl.handle.net/1807.1/167
Date: 2003-12

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