Abstract
Epimorphin/syntaxin-2 (EPM) is a plasma membrane-anchored protein that has at least two distinct functions depending on its membrane topology: vesicle fusion when localized to the cytoplasmic surface and morphogenic signaling when localized to the extracellular surface. Transgenic mice that express full-length extracellular EPM fused to the NH2-terminal signal sequence of interleukin-2, under the control of the whey acidic protein (WAP) gene promoter, exhibit aberrant mammary gland morphogenesis associated with increased expression of CCAAT enhancer binding protein beta (C/EBPbeta). Here we report that aged nulliparous and uniparous female WAP-EPM transgenic mice develop alveolar hyperplasias and well-differentiated adenocarcinomas that express high levels of C/EBPbeta, keratin-14, matrix metalloproteinase-3, and beta-catenin. This study reveals another pathway in which overexpression and alteration of a normal morphogenic process promote the development of cancer in the mammary gland.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenocarcinoma / genetics
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Adenocarcinoma / metabolism*
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Adenocarcinoma / pathology*
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Animals
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Biomarkers, Tumor / biosynthesis
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Biomarkers, Tumor / metabolism
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CCAAT-Enhancer-Binding Protein-beta / biosynthesis
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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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Female
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Hyperplasia / metabolism
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Hyperplasia / pathology
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Immunohistochemistry
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Male
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Mammary Glands, Animal / metabolism*
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Mammary Glands, Animal / pathology*
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Mammary Neoplasms, Experimental / genetics
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Mammary Neoplasms, Experimental / metabolism*
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Mammary Neoplasms, Experimental / pathology*
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Matrix Metalloproteinase 3 / biosynthesis
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Membrane Glycoproteins / biosynthesis*
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Membrane Glycoproteins / genetics
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Mice
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Mice, Transgenic
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Syntaxin 1 / biosynthesis
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Wnt Proteins / biosynthesis
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Wnt Proteins / metabolism
Substances
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Biomarkers, Tumor
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CCAAT-Enhancer-Binding Protein-beta
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Epim protein, mouse
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Membrane Glycoproteins
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Syntaxin 1
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Wnt Proteins
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Matrix Metalloproteinase 3