Inhibition of extracellular signal-regulated kinase1/2 activity of the breast cancer cell line MDA-MB-231 leads to major alterations in the pattern of protein expression

Biochemical and genetic strategies have implied that abberant signaling in the extracellular signal-regulated kinase (ERK)/mitogen-activated protein ( MAP) kinase pathway contributes significantly to transformed phenotypes. Us ing PD98059, an inhibitor of the ERK-kinase MEK1, we have here assessed the effects of ERK inhibition on the pattern of protein expression in the meta static human breast cancer cell line MDA-MB-231. At a concentration of inhi bitor which did not significantly affect cell growth, PD98059 induced large changes in the expression of MDA-MB-231 polypeptides. The majority of thes e changes were due to decreased expression of low-abundant proteins. Decrea ses of more abundant proteins such as glutathione-S-transferase pi, hsp80 a nd hsp100 were also recorded. The levels of a few proteins increased, among them cytokeratin 8. We conclude that PD98059 treatment of MDA-MB-231 cells induces large changes in protein expression.