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Isolation and characterization of DNA sequences amplified in multidrug-resistant hamster cells.
Open accessAbstract
The mechanism by which mammalian cells acquire resistance to chemotherapeutic agents has been investigated by using molecular genetic techniques. LZ and C5, two independently derived multidrug-resistant Chinese hamster cell lines, share specific amplified DNA sequences. We demonstrate that commonly amplified DNA sequences reside in a contiguous domain of approximately equal to 120 kilobases (kb). We report the isolation of this DNA domain in cosmid clones and show that the level of amplification of the domain is correlated with the level of resistance in multidrug-resistant cell lines. The organization of the amplified domain was deduced by a unique approach utilizing in-gel hybridization of cloned DNA with amplified genomic DNA. We show that the entire cloned region is amplified in adriamycin-resistant LZ cells and independently derived, colchicine-resistant C5 cells. A mRNA species of approximately equal to 5 kb is encoded by a gene located within the boundaries of this region. Genomic sequences homologous to the 5-kb mRNA span over 75 kb of the amplified DNA segment. The level of expression of this mRNA in multidrug-resistant cells is correlated with the degree of gene amplification and the degree of drug resistance. Our results strongly suggest that the 5-kb mRNA species plays a role in the mechanism of multidrug resistance common to the LZ and C5 cell lines.
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Cited by
Chen, C.-J., Chin, J. E., Ueda, K., Clark, D. P., Pastan, I., Gottesman, M. M., & Roninson, I. B. (1986) · Cell · doi:10.1016/0092-8674(86)90595-7 · Cited by 1,898
Self-citationRevisiting the role of ABC transporters in multidrug-resistant cancer
Robey, R. W., Pluchino, K. M., Hall, M. D., Fojo, A. T., Bates, S. E., & Gottesman, M. M. (2018) · Nature Reviews Cancer · doi:10.1038/s41568-018-0005-8 · Cited by 1,866
Expression of a multidrug-resistance gene in human tumors and tissues.
Fojo, A. T., Ueda, K., Slamon, D. J., Poplack, D. G., Gottesman, M. M., & Pastan, I. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.1.265 · Cited by 1,544
Isolation of human mdr DNA sequences amplified in multidrug-resistant KB carcinoma cells.
Roninson, I. B., Chin, J. E., Choi, K. G., Gros, P., Housman, D. E., Fojo, A., Shen, D. W., Gottesman, M. M., & Pastan, I. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.12.4538 · Cited by 686
Self-citationGENETIC ANALYSIS OF THE MULTIDRUG TRANSPORTER
Gottesman, M. M., Hrycyna, C. A., Schoenlein, P. V., Germann, U. A., & Pastan, I. (1995) · Annual Review of Genetics · doi:10.1146/annurev.ge.29.120195.003135 · Cited by 478
Metadata
- Authors
- Gros, P., Croop, J., Roninson, I., Varshavsky, A., & Housman, D. E.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1986-01
- Volume
- 83
- Issue
- 2
- Pages
- 337-341
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1968513798
- Cited by
- 222
- References
- 0
- FWCI
- 16.39
- Type
- journal article
- Language
- en
- Open access
- green
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- Gros, P., Croop, J., Roninson, I., Varshavsky, A., & Housman, D. E. (1986). Isolation and characterization of DNA sequences amplified in multidrug-resistant hamster cells. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.83.2.337
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