Common and distinct features of mammary tumors driven by Pten-deletion or activating Pik3ca mutation
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Jeff C. Liu1, Dong-Yu Wang2,3, Sean E. Egan4,5 and Eldad Zacksenhaus1,6
1 Division of Advanced Diagnostics, Toronto General Research Institute - University Health Network, Toronto, Ontario, Canada
2 Princess Margaret Cancer Center, Toronto, Ontario, Canada
3 Campbell Family Institute for Breast Cancer Research, Princess Margaret Hospital, Toronto, Ontario, Canada
4 Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada
5 Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
6 Department of Medicine, University of Toronto, Toronto, Ontario, Canada
Jeff C. Liu, email:
Eldad Zacksenhaus, email:
Keywords: PTEN, PIK3CA, breast cancer, bioinformatics, mouse models
Received: September 27, 2015 Accepted: January 18, 2016 Published: January 22, 2016
PTEN loss and PIK3CA activation both promote the accumulation of phosphatidylinositol (3, 4, 5)-trisphosphate (PIP3). While these proteins also have distinct biochemical functions, beyond the regulation of PIP3, little is known about the consequences of these differences in vivo. Here, we directly compared cancer signalling in mammary tumors from MMTV-Cre:Ptenf/f and MMTV-Cre:Pik3caLSL-H1047R mice. Using unsupervised hierarchical clustering we found that whereas MMTV-Cre:Pik3caLSL-H1047R-derived tumors fall into two separate groups, designated squamous-likeEx and class14Ex, MMTV-Cre:Ptenf/f tumors cluster as one group together with PIK3CAH1047R class14Ex, exhibiting a ‘luminal’ expression profile. Gene Set Enrichment Analysis (GSEA) of Pten∆ and PIK3CAH1047R class14Ex tumors revealed very similar profiles of signalling pathways as well as some interesting differences. Analysis of 18 signalling signatures revealed that PI3K signalling is significantly induced whereas EGFR signalling is significantly reduced in Pten∆ versus PIK3CAH1047R tumors. Thus, Pten∆ and PIK3CAH1047R tumors exhibit discernable differences that may impact tumorigenesis and response to therapy.
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