Zhao Jean J, Cheng Hailing, Jia Shidong, Wang Li, Gjoerup Ole V, Mikami Aki, Roberts Thomas M
Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16296-300. doi: 10.1073/pnas.0607899103. Epub 2006 Oct 23.
Growth factor signaling is mediated through Class IA phosphatidylinositol 3-kinases (PI3Ks). Among this class of enzymes, only p110alpha, encoded by the PIK3CA gene, has been found to be mutant in human cancers. To determine the specific functions of p110alpha, 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 p110alpha in these biological processes.
生长因子信号传导是通过IA类磷脂酰肌醇3-激酶（PI3K）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发生了突变。为了确定p110α的具体功能，我们构建了携带PIK3CA基因条件性靶向等位基因的小鼠。在此，我们报告PIK3CA基因敲除的小鼠胚胎成纤维细胞在对各种生长因子的细胞信号传导方面存在缺陷，无法分化为脂肪细胞，并且对多种致癌受体酪氨酸激酶诱导的致癌转化具有抗性，这表明p110α在这些生物学过程中具有重要作用。
