Occurrence of cytosolic protein and phosphoprotein changes in human colon tumor cells with the development of resistance to mitomycin C.
The cytosolic proteins and phosphoproteins of a mitomycin C-sensitive cell line were examined as progressively greater doses of mitomycin C were administered over a period of 44 weeks. Resistance of the human colon carcinoma cell line increased from a 50% inhibitory concentration of 1 to 6 microM over this time period. Changes in cytosolic protein patterns included increases in the amounts of three proteins with molecular weight X 10(-3)/apparent isoelectric point (Mr/pl) values of 56/6.2, 37/7.3, and 27/6.1. Analysis of in vitro 32P-labeled phosphoprotein patterns revealed reductions in the amounts of four proteins with Mr/pl values of 42/6.3, 40/6.7, 31/6.3, and 25/6.1. One increase was detected in a phosphoprotein with a Mr/pl value of 33/6.1. These changes in cytosolic components paralleled the development of resistance to mitomycin C and may reflect changes in the clonal composition of the cell line as it becomes progressively more resistant to mitomycin C or changes in critical proteins or enzymes involved in the activation or biotransformation of the drug.
D001345:Autoradiography; D002460:Cell Line; D003110:Colonic Neoplasms / Q000032:analysis*; D003600:Cytosol / Q000032:analysis*; D004351:Drug Resistance; D004591:Electrophoresis, Polyacrylamide Gel; D005982:Glutathione Transferase / Q000032:analysis; D006801:Humans; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000032:analysis*; D010750:Phosphoproteins / Q000032:analysis*
D008937:Mitomycins; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D016685:Mitomycin; D005982:Glutathione Transferase