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

The ErbB receptor tyrosine kinase family consists of the epidermal growth f actor (EGF) receptor (ErbBI) and three related receptors (ErbB2, ErbB3, Erb B4), Their intrinsic tyrosine kinases can be activated by receptor-dimeriza tion induced by numerous ligands or overexpression. ErbB receptors are freq uently overexpressed in breast cancer, and their overexpression is associat ed with protection from apoptosis. To directly assess their role in apoptos is sensitivity of breast cancer cells, we established MCF-7 breast carcinom a cell lines overexpressing each ErbB receptor alone or in all possible pai rs. Overexpression of ErbBI, ErbB2 and ErbB4 receptors was enough to activa te them as judged by their phosphorylation, whereas co-expression of other ErbB receptors was necessary for the phosphorylation of the ErbB3. Surprisi ngly, overexpression of the ErbB receptors even when combined with treatmen t with their ligands (EGF, transforming growth factor alpha, betacellulin, neuregulins) failed to protect the MCF-7 cells from cell death induced by e ither tumor necrosis factor (TNF) or serum starvation. During starvation TG F-alpha, however, increased the cell size of the ErbBI overexpressing cell line, and neuregulinI-beta I increased that of all cell lines. In conclusio n, our data does not support the role of ErbB receptors in the regulation o f cell death induced by TNF or serum starvation, and the observed associati on in breast cancer may be due to other concomitant changes. (C) 2000 Wiley -Liss, Inc.