Cell death induced by TNF or serum starvation is independent of ErbB receptor signaling in MCF-7 breast carcinoma cells

Egeblad, M., Jaattela, M. (June 2000) Cell death induced by TNF or serum starvation is independent of ErbB receptor signaling in MCF-7 breast carcinoma cells. International Journal of Cancer, 86 (5). pp. 617-25. ISSN 0020-7136 (Print)0020-7136

URL: http://www.ncbi.nlm.nih.gov/pubmed/10797281
DOI: 10.1002/(SICI)1097-0215(20000601)86:5<617::AID-IJC3>3.0.CO;2-Z

Abstract

The ErbB receptor tyrosine kinase family consists of the epidermal growth factor (EGF) receptor (ErbB1) and three related receptors (ErbB2, ErbB3, ErbB4). Their intrinsic tyrosine kinases can be activated by receptor-dimerization induced by numerous ligands or overexpression. ErbB receptors are frequently overexpressed in breast cancer, and their overexpression is associated with protection from apoptosis. To directly assess their role in apoptosis sensitivity of breast cancer cells, we established MCF-7 breast carcinoma cell lines overexpressing each ErbB receptor alone or in all possible pairs. Overexpression of ErbB1, ErbB2 and ErbB4 receptors was enough to activate them as judged by their phosphorylation, whereas co-expression of other ErbB receptors was necessary for the phosphorylation of the ErbB3. Surprisingly, overexpression of the ErbB receptors even when combined with treatment with their ligands (EGF, transforming growth factor alpha, betacellulin, neuregulins) failed to protect the MCF-7 cells from cell death induced by either tumor necrosis factor (TNF) or serum starvation. During starvation TGF-alpha, however, increased the cell size of the ErbB1 overexpressing cell line, and neuregulin1-beta1 increased that of all cell lines. In conclusion, our data does not support the role of ErbB receptors in the regulation of cell death induced by TNF or serum starvation, and the observed association in breast cancer may be due to other concomitant changes.

Item Type: Paper
Uncontrolled Keywords: Breast Neoplasms/*metabolism/pathology Cell Count/drug effects *Cell Death Cell Size/drug effects Culture Media, Serum-Free Female Humans Ligands Neuregulin-1/metabolism Phosphorylation Receptor, Epidermal Growth Factor/biosynthesis/*metabolism Receptor, erbB-2/biosynthesis/metabolism *Signal Transduction Transforming Growth Factor alpha/metabolism Tumor Cells, Cultured Tumor Necrosis Factor-alpha/*pharmacology Tyrosine/metabolism
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 > cell types and functions > cell functions > cell death
CSHL Authors:
Communities: CSHL labs > Egeblad lab
Depositing User: Matt Covey
Date: 1 June 2000
Date Deposited: 05 Dec 2014 14:57
Last Modified: 05 Dec 2014 14:57
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30951

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