| Expression of an activated Notch4(int-3) oncoprotein disrupts morphogenesis and induces an invasive phenotype in mammary epithelial cells in vitro. | |
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MedLine Citation:
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PMID: 10797286 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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J V Soriano; H Uyttendaele; J Kitajewski; R Montesano |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: International journal of cancer. Journal international du cancer Volume: 86 ISSN: 0020-7136 ISO Abbreviation: Int. J. Cancer Publication Date: 2000 Jun |
Date Detail:
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Created Date: 2000-06-08 Completed Date: 2000-06-08 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0042124 Medline TA: Int J Cancer Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 652-9 Citation Subset: IM |
Copyright Information:
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Copyright 2000 Wiley-Liss, Inc. |
Affiliation:
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Institute of Histology and Embryology, Department of Morphology, University of Geneva Medical Center, Geneva, Switzerland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Division / genetics Cell Transformation, Neoplastic* / genetics Cells, Cultured Epithelial Cells / cytology, physiology Female Mammary Glands, Animal / cytology*, pathology Mice Neoplasm Invasiveness Phenotype Proto-Oncogene Proteins / biosynthesis, genetics, physiology* Receptors, Cell Surface* Receptors, Notch |
| Grant Support | |
ID/Acronym/Agency:
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R01HL62454/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/NOTCH4 protein, human; 0/Proto-Oncogene Proteins; 0/Receptors, Cell Surface; 0/Receptors, Notch |
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