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.
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.
Seddighzadeh
M
M
Radiumhemmet's Research Laboratory, Department of Oncology and Pathology, Karolinska Institute and Hospital, Stockholm, Sweden.
Linder
S
S
Shoshan
M C
MC
Auer
G
G
Alaiya
A A
AA
D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D048369:MAP Kinase Kinase 1; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D010455:Peptides / Q000032:analysis; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D013382:Subtraction Technique; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology
D004791:Enzyme Inhibitors; D005419:Flavonoids; D009363:Neoplasm Proteins; D010455:Peptides; D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one