Initiating breast cancer by PIK3CA mutation.
PIK3CA mutations confer constitutive activation of PI3K, which initiates intracellular kinase signaling cascades that promote cell proliferation and survival. Recent studies by Meyer and colleagues, and Liu and colleagues demonstrate that expression of the H1047R exon 20 mutant of PIK3CA in luminal mammary epithelial cells induces tumorigenesis, implying that PIK3CA mutation is an early event in breast cancer. PIK3CA-H1047R-initiated tumors exhibit variable dependence on the oncogene and variable sensitivity to PI3K inhibition. Amplification of the oncogenes MYC and MET was observed in tumors that recurred following silencing of PIK3CA-H1047R, suggesting that these pathways represent mechanisms of escape from PI3K inhibition.
Department of Cancer Biology and Breast Cancer Research Program, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, VUMC, 2220 Pierce Avenue, 771 PRB, Nashville, TN 37232, USA. todd.miller@vanderbilt.edu
Todd W
TW
Miller
D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology / Q000235:genetics*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000201:enzymology / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D058534:Class I Phosphatidylinositol 3-Kinases; D005260:Female; D006801:Humans; D020125:Mutation, Missense; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*
D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human