title: Luminal expression of PIK3CA mutant H1047R in the mammary gland induces heterogeneous tumors.
abstract: 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.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Developmental and Molecular Pathways, Novartis Institutes for Biomedical Research, Basel, Switzerland.
authors.forename: Dominique S
authors.initials: DS
authors.lastname: Meyer
authors.forename: Heike
authors.initials: H
authors.lastname: Brinkhaus
authors.forename: Urs
authors.initials: U
authors.lastname: Müller
authors.forename: Matthias
authors.initials: M
authors.lastname: Müller
authors.forename: Robert D
authors.initials: RD
authors.lastname: Cardiff
authors.forename: Mohamed
authors.initials: M
authors.lastname: Bentires-Alj
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D058534:Class I Phosphatidylinositol 3-Kinases; D004847:Epithelial Cells / Q000201:enzymology / Q000473:pathology; D006801:Humans; D008321:Mammary Glands, Animal / Q000201:enzymology / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis / Q000235:genetics*; D011960:Receptors, Estrogen / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human