| Expression of the activated p185erbB2 tyrosine kinase in human epithelial cells leads to MAP kinase activation but does not confer oncogenicity. | |
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MedLine Citation:
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PMID: 9087165 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Amplification of the c-erbB2 gene and overexpression of p185erbB2 is found in approximately one-third of primary breast and ovarian cancers and also in some colon carcinomas. Moreover, a single point mutation in erbB2(V 664 E) confers transforming potential to erbB2 in NIH3T3 cells, even when expressed at low levels. To examine the transformation potential of erbB2 or erbB2(V-E) in colon epithelial cells, we have transfected a nontumorigenic clone of SW 613-S cells with either wild-type p185erbB2 or mutated p185erbB2(V-E). In contrast to p185erbB2, p185erbB2(V-E) associated constitutively with members of the Shc protein family, leading to phosphorylation of Shc and to stimulation of mitogen-activated protein kinase (MAP kinase). However, constitutive activation of MAP kinase activation in p185erbB2(V-E) expressing cells did not result in a tumorigenic phenotype. In addition, p185erbB2(V-E) expressing cells displayed a reduced ability to grow in soft agar compared to the parental cell line. In contrast these transfected cells were able to grow in three-dimensional collagen gels, whereas parental cells were not. Thus, expression of erbB2(V-E) in SW 613-S cells induced multiple changes in intracellular signaling and in growth requirement phenotype, particularly in response to the extracellular environment. |
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Authors:
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F Nowak; A Jacquemin-Sablon; J Pierre |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Experimental cell research Volume: 231 ISSN: 0014-4827 ISO Abbreviation: Exp. Cell Res. Publication Date: 1997 Mar |
Date Detail:
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Created Date: 1997-04-29 Completed Date: 1997-04-29 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0373226 Medline TA: Exp Cell Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 251-9 Citation Subset: IM |
Affiliation:
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Faculté de Pharmacie, INSERM U 461, Châtenay Malabry, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adaptor Proteins, Signal Transducing* Adaptor Proteins, Vesicular Transport* Adenocarcinoma / enzymology*, pathology Animals Calcium-Calmodulin-Dependent Protein Kinases / metabolism* Cell Differentiation / drug effects Cell Division / drug effects Cell Transformation, Neoplastic Collagen Colonic Neoplasms / enzymology*, pathology Enzyme Activation Enzyme Induction / drug effects Epidermal Growth Factor / pharmacology Epithelial Cells Epithelium / enzymology Female Gels Humans Intestinal Mucosa / drug effects, enzymology*, pathology Mice Neoplasm Proteins / biosynthesis*, genetics, physiology Neoplasm Transplantation Oncogenes Phosphorylation Point Mutation Protein Processing, Post-Translational Proteins / metabolism Receptor, erbB-2 / biosynthesis*, genetics, physiology Recombinant Fusion Proteins / physiology Shc Signaling Adaptor Proteins Transfection Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
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0/Adaptor Proteins, Signal Transducing; 0/Adaptor Proteins, Vesicular Transport; 0/Gels; 0/Neoplasm Proteins; 0/Proteins; 0/Recombinant Fusion Proteins; 0/SHC1 protein, human; 0/Shc Signaling Adaptor Proteins; 0/Shc1 protein, mouse; 62229-50-9/Epidermal Growth Factor; 9007-34-5/Collagen; EC 2.7.10.1/Receptor, erbB-2; EC 2.7.11.17/Calcium-Calmodulin-Dependent Protein Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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