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Background  The PI3K/AKT pathway plays a pivotal role in breast cancer development and maintenance.  PIK3CA , encoding the PI3K catalytic subunit, is the oncogene exhibiting a high frequency of gain-of-function mutations leading to PI3K/AKT pathway activation in breast cancer.  PIK3CA  mutations have been observed in 30% to 40% of ERα-positive breast tumors. However the physiopathological role of  PIK3CA  mutations in breast tumorigenesis remains largely unclear.    Methodology/Principal Findings  To identify relevant downstream target genes and signaling activated by aberrant PI3K/AKT pathway in breast tumors, we first analyzed gene expression with a pangenomic oligonucleotide microarray in a series of 43 ERα-positive tumors with and without  PIK3CA  mutations. Genes of interest were then investigated in 249 ERα-positive breast tumors by real-time quantitative RT-PCR. A robust collection of 19 genes was found to be differently expressed in  PIK3CA- mutated tumors.  PIK3CA  mutations were associated with over-expression of several genes involved in the Wnt signaling pathway ( WNT5A ,  TCF7L2 ,  MSX2 ,  TNFRSF11B ), regulation of gene transcription ( SEC14L2 ,  MSX2 ,  TFAP2B ,  NRIP3 ) and metal ion binding ( CYP4Z1 ,  CYP4Z2P ,  SLC40A1 ,  LTF ,  LIMCH1 ).    Conclusion/Significance  This new gene set should help to understand the behavior of  PIK3CA -mutated cancers and detailed knowledge of Wnt signaling activation could lead to novel therapeutic strategies.

Gene Expression Profiling Reveals New Aspects of PIK3CA Mutation in ERalpha-Positive Breast Cancer: Major Implication of the Wnt Signaling Pathway