Insulin-like growth factor-II regulates PTEN expression in the mammary gland
Insulin-like growth factor-II regulates PTEN expression in the mammary gland
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DOI：
10.1074/jbc.m306894200
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发表时间：
2003-12-12
影响因子：
4.8
通讯作者：
Khokha, R
中科院分区：
文献类型：
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作者：
Moorehead, RA;Hojilla, CV;Khokha, R
肿瘤抑制因子PTEN在包括乳腺癌在内的许多癌症中发生改变，但已知只有少数因素控制其表达。PTEN通过调节磷脂酰肌醇3激酶（PI3K）通路的关键组分Akt磷酸化，在细胞存活和增殖中发挥重要作用。本研究表明，胰岛素样生长因子- ii （IGF-II）通过PI3K发出信号，调节乳腺中PTEN的表达。小鼠乳腺注射IGF-II可显著提高PTEN的表达。转基因IGF-II的表达也增加了乳腺PTEN蛋白，导致Akt磷酸化、上皮细胞增殖和乳腺形态发生的减少。IGF-II诱导PTEN启动子活性和蛋白水平，这涉及直接早期基因egr-1。因此，我们在PI3K通路中发现了一个新的负反馈回路，其中IGF-II诱导PTEN表达来调节其生理效应。
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.