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 ov...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1985-09, Vol.45 (9), p.4422-4427
Main Authors: TAYLOR, C. W, BRATTAIN, M. G, YEOMAN, L. C
Format: Article
Language:English
Subjects:
Antineoplastic agents
Autoradiography
Biological and medical sciences
Cell Line
Colonic Neoplasms - analysis
Cytosol - analysis
Drug Resistance
Electrophoresis, Polyacrylamide Gel
General aspects
Glutathione Transferase - analysis
Humans
Medical sciences
Mitomycin
Mitomycins - pharmacology
Neoplasm Proteins - analysis
Pharmacology. Drug treatments
Phosphoproteins - analysis
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Summary: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.
ISSN:0008-5472
1538-7445