Epimorphin overexpression in the mouse mammary gland promotes alveolar hyperplasia and mammary adenocarcinoma.
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.
Bascom
Jamie L
JL
Life Science Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
Fata
Jimmie E
JE
Hirai
Yohei
Y
Sternlicht
Mark D
MD
Bissell
Mina J
MJ
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000378:metabolism; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000096:biosynthesis; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D008321:Mammary Glands, Animal / Q000378:metabolism* / Q000473:pathology*; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D050827:Syntaxin 1 / Q000096:biosynthesis; D051153:Wnt Proteins / Q000096:biosynthesis / Q000378:metabolism
D014408:Biomarkers, Tumor; D022782:CCAAT-Enhancer-Binding Protein-beta; C504582:Epim protein, mouse; D008562:Membrane Glycoproteins; D050827:Syntaxin 1; D051153:Wnt Proteins; D019278:Matrix Metalloproteinase 3