Insulin-like growth factor-II regulates PTEN expression in the mammary gland |
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Authors: | Moorehead Roger A Hojilla Carlo V De Belle Ian Wood Geoffrey A Fata Jimmie E Adamson Eileen D Watson Katrina L M Edwards Dylan R Khokha Rama |
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Affiliation: | Ontario Cancer Institute/University Health Network, University of Toronto, Toronto, Ontario M5G 2M9, Canada. |
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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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