Egeblad, M., Mortensen, O. H., Jaattela, M. (October 2001) Truncated ErbB2 receptor enhances ErbB1 signaling and induces reversible, ERK-independent loss of epithelial morphology. International Journal of Cancer, 94 (2). pp. 185-91. ISSN 0020-7136 (Print)0020-7136
Abstract
Shedding of the extracellular domain of the ErbB2 tyrosine kinase receptor and expression of the remaining NH(2)-terminally truncated ErbB2 correlates with lymph node metastases and adverse outcome in human breast cancer. To study the possible signaling from such a truncated receptor, MCF-7 human breast cancer cells expressing NH(2)-terminally truncated ErbB2 (DeltaNErbB2) were compared with cells overexpressing wild-type ErbB2. Expression of DeltaNErbB2 in MCF-7 cells resulted in sustained activation of extracellular signal-regulated kinases (ERK) 1/2, extensive loss of the epithelial morphology, appearance of vesicles and long protrusions as well as pronounced scattering of the cells. Similar alterations were observed upon ErbB2 overexpression but at much lower levels. Employing cell clones with inducible expression of DeltaNErbB2, it was revealed that the morphological changes were fully reversible and depended on continuous expression of DeltaNErbB2 but not on the activation of the ERK1/2 pathway. Interestingly, the expression of DeltaNErbB2 resulted also in the increased expression and phosphorylation of ErbB1 as well as in the prolonged ligand-induced activation of the ErbB1 signaling pathway. In conclusion, constitutive signaling upon expression of the truncated ErbB2 receptor in human breast cancer cells promotes morphological changes indicative of a more motile and aggressive phenotype.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Breast Neoplasms/*pathology Enzyme Activation Epidermal Growth Factor/pharmacology Epithelial Cells/pathology Female Humans Mitogen-Activated Protein Kinases/*physiology Receptor, Epidermal Growth Factor/*physiology Receptor, erbB-2/chemistry/*physiology Tumor Cells, Cultured |
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > ErbB diseases & disorders > cancer > cancer types > breast cancer organs, tissues, organelles, cell types and functions > tissues types and functions > epithelia |
| CSHL Authors: | |
| Communities: | CSHL labs > Egeblad lab |
| Depositing User: | Matt Covey |
| Date: | 15 October 2001 |
| Date Deposited: | 05 Dec 2014 16:25 |
| Last Modified: | 05 Dec 2014 16:25 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/30952 |
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