High tumor incidence and activation of the PI3K/AKT pathway in transgenic mice define AIB1 as an oncogene
High tumor incidence and activation of the PI3K/AKT pathway in transgenic mice define AIB1 as an oncogene
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DOI：
10.1016/j.ccr.2004.06.027
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发表时间：
2004-09-01
期刊：
影响因子：
50.3
通讯作者：
Brown, M
中科院分区：
文献类型：
--
作者：
Torres-Arzayus, MI;de Mora, JF;Brown, M
编码AIB1的基因，一种雌激素受体辅激活因子，在人类乳腺癌的一个亚群中被扩增。本研究表明，转基因小鼠AIB1-tg的过表达可导致乳腺肥大、增生、断奶后不正常复旧和恶性乳腺肿瘤的发生。其他器官的肿瘤也增加，包括垂体和子宫。AIB1过表达增加乳腺IGF-I mRNA和血清IGF-I蛋白水平。此外，来源于AIB1-tg小鼠的原代乳腺上皮细胞和乳腺肿瘤细胞中，IGF-I受体和下游信号分子被激活。在培养的AIB1-tg乳腺肿瘤细胞中，敲低AIB1表达导致IGF-I mRNA水平降低，细胞凋亡增加，提示自分泌IGF-I环是AIB1诱导肿瘤发生的机制基础。
The gene encoding AIB1, an estrogen receptor coactivator, is amplified in a subset of human breast cancers. Here we show that overexpression of AIB1 in transgenic mice (AIB1-tg) leads to mammary hypertrophy, hyperplasia, abnormal postweaning involution, and the development of malignant mammary tumors. Tumors are also increased in other organs, including the pituitary and uterus. AIB1 overexpression increases mammary IGF-I mRNA and serum IGF-I protein levels. In addition, IGF-I receptor and downstream signaling molecules are activated in primary mammary epithelial cells and mammary tumor cells derived from AIB1-tg mice. Knockdown of AIB1 expression in cultured AIB1-tg mammary tumor cells leads to reduced IGF-I mRNA levels and increased apoptosis, suggesting that an autocrine IGF-I loop underlies the mechanism of AIB1-induced oncogenesis.