Occurrence of cytosolic protein and phosphoprotein changes in human colon tumor cells with the development of resistance to mitomycin C

Cancer Res. 1985 Sep;45(9):4422-7.

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 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Autoradiography
  • Cell Line
  • Colonic Neoplasms / analysis*
  • Cytosol / analysis*
  • Drug Resistance
  • Electrophoresis, Polyacrylamide Gel
  • Glutathione Transferase / analysis
  • Humans
  • Mitomycin
  • Mitomycins / pharmacology*
  • Neoplasm Proteins / analysis*
  • Phosphoproteins / analysis*

Substances

  • Mitomycins
  • Neoplasm Proteins
  • Phosphoproteins
  • Mitomycin
  • Glutathione Transferase