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Title

Expression of an activated Notch4(int-3) oncoprotein disrupts morphogenesis and induces an invasive phenotype in mammary epithelial cells in vitro

Authors
Soriano, Jesus
Uyttendaele, Hendrik
Kitajewski, Jan
Published in International Journal of Cancer. 2000, vol. 86, no. 5, p. 652-9
Abstract The protein encoded by the Notch4 gene is a member of the Notch/lin-12 family of transmembrane receptor proteins, which have been shown to control cell fate determination and cell differentiation in a wide variety of organisms. Expression of Notch4(int-3), a truncated form of Notch4 having most of its extracellular domain deleted, as a transgene in mice induces the formation of poorly differentiated mammary carcinomas. To establish whether Notch4(int-3) has the capacity of subverting normal epithelial architecture, we assessed the effect of Notch4(int-3) expression on the in vitro morphogenetic properties of TAC-2 mammary epithelial cells. When grown in three-dimensional collagen gels in the presence of hydrocortisone, both wild-type and LacZ-transfected TAC-2 cells formed alveolar-like structures composed of polarized epithelial cells surrounding a central lumen. In contrast, TAC-2 cells programmed to express Notch4(int-3) formed compact cell aggregates devoid of tissue-specific organization. In addition, when grown on the surface of a collagen gel, Notch4(int-3)-expressing TAC-2 cells invaded the underlying matrix, whereas TAC-2 LacZ cells remained strictly confined to the gel surface. Expression of Notch4(int-3) in TAC-2 cells also disrupted contact-inhibition of cell proliferation, resulting in cell multilayering. Our results suggest that the ability of Notch4(int-3) to subvert normal epithelial morphogenesis and to promote invasion of the extracellular matrix contributes significantly to its tumorigenic potential.
Keywords AnimalsCell Division/geneticsCell Transformation, Neoplastic/geneticsCells, CulturedEpithelial Cells/cytology/physiologyFemaleMammary Glands, Animal/cytology/pathologyMiceNeoplasm InvasivenessPhenotypeProto-Oncogene Proteins/biosynthesis/genetics/physiologyReceptors, Cell SurfaceReceptors, Notch
Identifiers
PMID: 10797286
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SORIANO, Jesus et al. Expression of an activated Notch4(int-3) oncoprotein disrupts morphogenesis and induces an invasive phenotype in mammary epithelial cells in vitro. In: International Journal of Cancer, 2000, vol. 86, n° 5, p. 652-9. https://archive-ouverte.unige.ch/unige:3858

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Deposited on : 2009-10-22

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