The p110α isoform of PI3K is essential for proper growth factor signaling and oncogenic transformation
The p110α isoform of PI3K is essential for proper growth factor signaling and oncogenic transformation
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DOI：
10.1073/pnas.0607899103
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发表时间：
2006-10-31
影响因子：
11.1
通讯作者：
Roberts, Thomas M.
中科院分区：
文献类型：
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作者：
Zhao, Jean J.;Cheng, Hailing;Roberts, Thomas M.
生长因子信号是通过IA类磷脂酰肌醇3-激酶(PI3Ks)介导的。在这类酶中，只有由PIK3CA基因编码的p110α在人类癌症中被发现是突变的。为了确定p110α的特定功能，我们产生了携带PIK3CA基因的条件靶向等位基因的小鼠。在此，我们报道了PIK3CA基因敲除的小鼠胚胎成纤维细胞对各种生长因子的反应缺乏细胞信号，不能分化为脂肪细胞，并且对多种致癌受体酪氨酸激酶诱导的致癌转化具有抵抗力，表明p110α在这些生物学过程中起着重要作用。
Growth factor signaling is mediated through Class IA phosphatidylinositol 3-kinases (PI3Ks). Among this class of enzymes, only p110 alpha, encoded by the PIK3CA gene, has been found to be mutant in human cancers. To determine the specific functions of p110 alpha, we generated mice carrying a conditionally targeted allele of the PIK3CA gene. Here, we report that PIK3CA-knockout mouse embryonic fibroblasts are deficient in cellular signaling in response to various growth factors, unable to differentiate into adipocytes, and resistant to oncogenic transformation induced by a variety of oncogenic receptor tyrosine kinases, indicating a fundamental role for p110 alpha in these biological processes.