Friedrich Miescher Institute for Biomedical Research, Developmental and Molecular Pathways, Novartis Institutes for Biomedical Research, Basel, Switzerland.
Cancer Res. 2011 Jul 1;71(13):4344-51. doi: 10.1158/0008-5472.CAN-10-3827. Epub 2011 Apr 11.
The phosphoinositide 3-kinase (PI3K) signaling cascade, a key mediator of cellular survival, growth, and metabolism, is frequently altered in human cancer. Activating mutations in PIK3CA, which encodes the α-catalytic subunit of PI3K, occur in approximately 30% of breast cancers. These mutations result in constitutive activity of the enzyme and are oncogenic, but it is not known whether they are sufficient to induce mammary carcinomas in mice. In the present study, we show that the expression of mutant PIK3CA H1047R in the luminal mammary epithelium evokes heterogeneous tumors that express luminal and basal markers and are positive for the estrogen receptor. Our results suggest that the PIK3CA H1047R oncogene targets a multipotent progenitor cell and, furthermore, show that this model recapitulates features of human breast tumors with PIK3CA H1047R.
磷酸肌醇 3-激酶 (PI3K) 信号级联是细胞存活、生长和代谢的关键介质，在人类癌症中经常发生改变。编码 PI3K 的 α-催化亚基的 PIK3CA 中的激活突变约发生在 30%的乳腺癌中。这些突变导致酶的组成性活性和致癌性，但尚不清楚它们是否足以在小鼠中诱导乳腺肿瘤。在本研究中，我们表明，突变型 PIK3CA H1047R 在腔上皮中的表达引发了异质性肿瘤，这些肿瘤表达腔和基底标志物，并对雌激素受体呈阳性。我们的结果表明，PIK3CA H1047R 癌基因靶向多能祖细胞，并且还表明该模型再现了具有 PIK3CA H1047R 的人类乳腺肿瘤的特征。
