Characterization of Wnt-1 and Wnt-2 induced growth alterations and signaling pathways in NIH3T3 fibroblasts.
Members of the Wnt family induce mouse mammary tumors and partially transform mammary epithelial cells in culture. However, their mechanism of transformation remains to be elucidated. In NIH3T3 mouse embryo fibroblasts, a standard transformation model, Wnt-1 and Wnt-2 were shown to induce altered properties including increased saturation density and growth in soft agar. Such cells also exhibited increased cell-cell adhesiveness. However, unlike oncogenes such as PDGFB or ras, Wnt-1 and -2 failed to induce detectable transformed foci following transfection, and stable NIH3T3 transfectants lacked tumor forming capacity. Wnt-1 and -2 transfectants exhibited increased uncomplexed, cytosolic beta-catenin, which was not observed with PDGFB, ras or erbB2 transfectants. In transient transfection, Wnt-1 and -2 induced a rapid increase in cytosolic beta-catenin but no detectable increase in the phosphorylated activated forms of MAP kinase. In contrast, ras was a potent activator of MAP kinase but had no effect on free beta-catenin levels. These findings establish that both Wnt signaling and pattern of growth alterations differ from those of oncogenes which activate proliferative signaling pathways in NIH3T3 cells.
Bafico
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Derald H Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, NY 10029, USA.
Gazit
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Wu-Morgan
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Yaniv
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Aaronson
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D016475:3T3 Cells; D000818:Animals; D002448:Cell Adhesion; D002455:Cell Division; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D006801:Humans; D051379:Mice; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014162:Transfection; D051153:Wnt Proteins; D051155:Wnt1 Protein; D051154:Wnt2 Protein; D029961:Zebrafish Proteins
D011518:Proto-Oncogene Proteins; C495247:WNT1 protein, human; C495244:WNT2 protein, human; D051153:Wnt Proteins; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D051154:Wnt2 Protein; D029961:Zebrafish Proteins