Epithelial Pten is dispensable for intestinal homeostasis but suppresses adenoma development and progression after Apc mutation
Epithelial Pten is dispensable for intestinal homeostasis but suppresses adenoma development and progression after Apc mutation
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DOI：
10.1038/ng.256
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发表时间：
2008-12-01
期刊：
影响因子：
30.8
通讯作者：
Clarke, Alan R.
中科院分区：
文献类型：
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作者：
Marsh, Victoria;Winton, Douglas J.;Clarke, Alan R.
PTEN在一系列组织类型中充当肿瘤抑制因子，并且已经涉及肠干细胞的调节。为了研究Pten在肠道中的功能，我们使用了各种条件性转基因策略来特异性地从小鼠肠上皮中删除Pten。我们表明，Pten损失，特别是在成人或胚胎上皮细胞群不影响正常的结构或上皮的稳态。然而，Pten在Apc缺陷的情况下的损失通过Akt的活化增加而加速肿瘤发生，导致腺癌的快速发展。我们的结论是，Pten是多余的，否则正常的肠上皮和上皮干细胞，但在激活的Wnt信号的背景下，抑制腺癌的进展，通过调节激活Akt水平。
PTEN acts as a tumor suppressor in a range of tissue types and has been implicated in the regulation of intestinal stem cells. To study Pten function in the intestine, we used various conditional transgenic strategies to specifically delete Pten from the mouse intestinal epithelium. We show that Pten loss specifically within the adult or embryonic epithelial cell population does not affect the normal architecture or homeostasis of the epithelium. However, loss of Pten in the context of Apc deficiency accelerates tumorigenesis through increased activation of Akt, leading to rapid development of adenocarcinoma. We conclude that Pten is redundant in otherwise normal intestinal epithelium and epithelial stem cells but, in the context of activated Wnt signaling, suppresses progression to adenocarcinoma through modulation of activated Akt levels.