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.
©2011 AACR.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Biomarkers, Tumor / biosynthesis
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Biomarkers, Tumor / genetics
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Cell Transformation, Neoplastic / genetics*
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Cell Transformation, Neoplastic / metabolism
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Cell Transformation, Neoplastic / pathology
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Class I Phosphatidylinositol 3-Kinases
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Epithelial Cells / enzymology
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Epithelial Cells / pathology
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Humans
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Mammary Glands, Animal / enzymology
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Mammary Glands, Animal / pathology
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Mammary Neoplasms, Experimental / enzymology
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Mammary Neoplasms, Experimental / genetics*
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Mammary Neoplasms, Experimental / pathology
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Mice
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Mice, Inbred BALB C
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Mice, Transgenic
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Mutation
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Phosphatidylinositol 3-Kinases / biosynthesis
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Phosphatidylinositol 3-Kinases / genetics*
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Receptors, Estrogen / biosynthesis
Substances
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Biomarkers, Tumor
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Receptors, Estrogen
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Phosphatidylinositol 3-Kinases
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Class I Phosphatidylinositol 3-Kinases
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PIK3CA protein, human