Somatic mutation and gain of copy number of PIK3CA in human breast cancer

作者：Guojun Wu, Mingzhao Xing, Elizabeth Mambo, Xin Hua Huang, Junwei Liu, Zhongmin Guo, Aditi Chatterjee, David Goldenberg, Susanne M. Gollin, Saraswati Sukumar, Barry Trink, David Sidransky · 发表于：Breast Cancer Research · 年份：2005 · DOI：10.1186/bcr1262 · 被引用次数：228 · 研究领域：PI3K/AKT/mTOR signaling in cancer、Microtubule and mitosis dynamics、Biological Research and Disease Studies

INTRODUCTION: Phosphatidylinositol 3-kinases (PI3Ks) are a group of lipid kinases that regulate signaling pathways involved in cell proliferation, adhesion, survival, and motility. Even though PIK3CA amplification and somatic mutation have been reported previously in various kinds of human cancers, the genetic change in PIK3CA in human breast cancer has not been clearly identified. METHODS: Fifteen breast cancer cell lines and 92 primary breast tumors (33 with matched normal tissue) were used to check somatic mutation and gene copy number of PIK3CA. For the somatic mutation study, we specifically checked exons 1, 9, and 20, which have been reported to be hot spots in colon cancer. For the analysis of the gene copy number, we used quantitative real-time PCR and fluorescence in situ hybridization. We also treated several breast cancer cells with the PIK3CA inhibitor LY294002 and compared the apoptosis status in cells with and without PIK3CA mutation. RESULTS: We identified a 20.6% (19 of 92) and 33.3% (5 of 15) PIK3CA somatic mutation frequency in primary breast tumors and cell lines, respectively. We also found that 8.7% (8 of 92) of the tumors harbored a gain of PIK3CA gene copy number. Only four cases in this study contained both an increase in the gene copy number and a somatic mutation. In addition, mutation of PIK3CA correlated with the status of Akt phosphorylation in some breast cancer cells and inhibition of PIK3CA-induced increased apoptosis in breast cancer cells wit...