OCCURRENCE OF CYTOSOLIC PROTEIN AND PHOSPHOPROTEIN CHANGES IN HUMAN-COLON TUMOR-CELLS WITH THE DEVELOPMENT OF RESISTANCE TO MITOMYCIN C-1

  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (9) , 4422-4427
Abstract
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 .mu.M over this time period. Changes in cytosolic protein patterns included increases in the amounts of three proteins with molecular weight .times. 10-3/ apparent isoelectric point (Mr/pI) 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/pI 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/pI 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.