Reverse transformation of multidrug-resistant cells
- 1 January 1994
- journal article
- Published by Springer Nature in Cancer and Metastasis Reviews
- Vol. 13 (2), 191-207
- https://doi.org/10.1007/bf00689636
Abstract
Spontaneously transformed Chinese hamster lung cells with high levels of resistance (˜ 100-fold to 70,000-fold) to actinomycin D, daunorubicin, or vincristine exhibit morphology and growth patterns characteristic of normal cellsin vitro and reduced tumorigenicityin vivo. These reverse transformed, multidrug-resistant cells amplify and highly overexpress one or more genes encoding P-glycoprotein. Similarly, hydrocarbon-induced mouse sarcoma cells selected with actinomycin D, vincristine, or ethidium bromide developed high levels of resistance associated with reduced drug accumulation and suppression of malignancy. To determine whether human tumor cells would undergo similar changes and whether reverse transformation reflected an altered state of differentiation, nine multidrug-resistant sublines were selected with four agents from human neuroblastoma cells with well defined pathways of differentiation. Those five with resistance levels above about 125-fold showed a reduced tumor frequency as compared to control cells. All resistant sublines showed altered differentiation. The changes in transformation phenotype appear to be intrinsic and not the result of altered immunogenicity. Two additional consequences of high level multidrug resistance have been observed: change in ganglioside composition in the Chinese hamster cells, manifested as a block in higher ganglioside biosynthesis and/or a relative increase in GM3, and increase in epidermal growth factor receptor in all three cell systems. A tentative hypothesis links ganglioside and growth factor receptor changes to the change in transformation phenotype. The basis of the reverse transformation phenomenon is not known, but the major alterations in expression of P-glycoprotein, gangliosides, and the epidermal growth factor receptor implicate, in some way, the plasma membrane.Keywords
This publication has 35 references indexed in Scilit:
- BIOCHEMISTRY OF MULTIDRUG RESISTANCE MEDIATED BY THE MULTIDRUG TRANSPORTERAnnual Review of Biochemistry, 1993
- Genetic aspects of multidrug resistanceCancer, 1992
- Molecular and Cellular Biology of Multidrug Resistance in Tumor CellsPublished by Springer Nature ,1991
- THE BIOCHEMISTRY OF P-GLYCOPROTEIN-MEDIATED MULTIDRUG RESISTANCEAnnual Review of Biochemistry, 1989
- Biochemical and karyological properties of cells resistant to the quinazoline antifolate, methasquinEuropean Journal of Cancer (1965), 1978
- Amplification of Dihydrofolate Reductase Genes in Methotrexate-resistant Cultured Mouse CellsCold Spring Harbor Symposia on Quantitative Biology, 1978
- Metaphase Chromosome Anomaly: Association with Drug Resistance and Cell-Specific ProductsScience, 1976
- SOME BIOCHEMICAL PROPERTIES OF CHINESE HAMSTER CELLS SENSITIVE AND RESISTANT TO ACTINOMYCIN DThe Journal of cell biology, 1974
- Reduced permeability in CHO cells as a mechanism of resistance to colchicineJournal of Cellular Physiology, 1974
- Incorporation of Tritiated Actinomycin D into Drug-Sensitive and Drug-Resistant HeLa CellsScience, 1966