Inhibition of extracellular signal-regulated kinase 1/2 activity of the breast cancer cell line MDA-MB-231 leads to major alterations in the pattern of protein expression

• Published in: Electrophoresis 2000-07, Vol.21 (13), p.2737-2743
• Main Authors: Seddighzadeh, M, Linder, S, Shoshan, M C, Auer, G, Alaiya, A A
• Format: Article
• Language: English
• Subjects: Breast Neoplasms - enzymology; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cell Division - drug effects; Dose-Response Relationship, Drug; Electrophoresis, Gel, Two-Dimensional; Enzyme Inhibitors - pharmacology; Female; Flavonoids - pharmacology; Gene Expression Profiling; Gene Expression Regulation, Neoplastic - drug effects; Humans; MAP Kinase Kinase 1; MAP Kinase Signaling System - drug effects; Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors; Mitogen-Activated Protein Kinase 1 - physiology; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - physiology; Neoplasm Metastasis; Neoplasm Proteins - antagonists & inhibitors; Neoplasm Proteins - physiology; Peptides - analysis; Phosphorylation - drug effects; Protein Processing, Post-Translational - drug effects; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Subtraction Technique; Tumor Cells, Cultured - drug effects; Tumor Cells, Cultured - enzymology
• ISSN: 0173-0835
• DOI: 10.1002/1522-2683(20000701)21:13<2737::AID-ELPS2737>3.0.CO;2-2

Biochemical and genetic strategies have implied that aberrant signaling in the extracellular signal-regulated kinase (ERK)/mitogen-activated protein (MAP) kinase pathway contributes significantly to transformed phenotypes. Using 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 metastatic human breast cancer cell line MDA-MB-231. At a concentration of inhibitor which did not significantly affect cell growth, PD98059 induced large changes in the expression of MDA-MB-231 polypeptides. The majority of these changes were due to decreased expression of low-abundance proteins. Decreases of more abundant proteins such as glutathione-S-transferase pi, hsp80 and 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.