|Expression of the activated p185erbB2 tyrosine kinase in human epithelial cells leads to MAP kinase activation but does not confer oncogenicity.|
|PMID: 9087165 Owner: NLM Status: MEDLINE|
|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.|
|F Nowak; A Jacquemin-Sablon; J Pierre|
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|Type: Journal Article; Research Support, Non-U.S. Gov't|
|Title: Experimental cell research Volume: 231 ISSN: 0014-4827 ISO Abbreviation: Exp. Cell Res. Publication Date: 1997 Mar|
|Created Date: 1997-04-29 Completed Date: 1997-04-29 Revised Date: 2009-11-19|
Medline Journal Info:
|Nlm Unique ID: 0373226 Medline TA: Exp Cell Res Country: UNITED STATES|
|Languages: eng Pagination: 251-9 Citation Subset: IM|
|Faculté de Pharmacie, INSERM U 461, Châtenay Malabry, France.|
|APA/MLA Format Download EndNote Download BibTex|
Adaptor Proteins, Signal Transducing*
Adaptor Proteins, Vesicular Transport*
Adenocarcinoma / enzymology*, pathology
Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
Cell Differentiation / drug effects
Cell Division / drug effects
Cell Transformation, Neoplastic
Colonic Neoplasms / enzymology*, pathology
Enzyme Induction / drug effects
Epidermal Growth Factor / pharmacology
Epithelium / enzymology
Intestinal Mucosa / drug effects, enzymology*, pathology
Neoplasm Proteins / biosynthesis*, genetics, physiology
Protein Processing, Post-Translational
Proteins / metabolism
Receptor, erbB-2 / biosynthesis*, genetics, physiology
Recombinant Fusion Proteins / physiology
Shc Signaling Adaptor Proteins
Tumor Cells, Cultured
|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 22.214.171.124/Receptor, erbB-2; EC 126.96.36.199/Calcium-Calmodulin-Dependent Protein Kinases|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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