M. Egeblad et J. Jaattela, Cell death induced by TNF or serum starvation is independent of ErbB receptor signaling in MCF-7 breast carcinoma cells, INT J CANC, 86(5), 2000, pp. 617-625
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.