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Expression of a full-length cDNA for the human "MDR1" gene confers resistance to colchicine, doxorubicin, and vinblastine.
Open accessAbstract
Intrinsic and acquired multidrug resistance (MDR) is an important problem in cancer therapy. MDR in human KB carcinoma cells selected for resistance to colchicine, vinblastine, or doxorubicin (former generic name adriamycin) is associated with overexpression of the "MDR1" gene, which encodes P-glycoprotein. We previously have isolated an overlapping set of cDNA clones for the human MDR1 gene from multidrug-resistant KB cells. Here we report the construction of a full-length cDNA for the human MDR1 gene and show that this reconstructed cDNA, when inserted into a retroviral expression vector containing the long terminal repeats of Moloney leukemia virus or Harvey sarcoma virus, functions in mouse NIH 3T3 and human KB cells to confer the complete multidrug-resistance phenotype. These results suggest that the human MDR1 gene may be used as a positive selectable marker to introduce genes into human cells and to transform human cells to multidrug resistance without introducing nonhuman antigens.
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Cited by
Multidrug resistance in cancer: role of ATP–dependent transporters
Gottesman, M. M., Fojo, T., & Bates, S. E. (2002) · Nature Reviews Cancer · doi:10.1038/nrc706 · Cited by 5,536
Self-citationTargeting multidrug resistance in cancer
Szakács, G., Paterson, J. K., Ludwig, J. A., Booth-Genthe, C., & Gottesman, M. M. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd1984 · Cited by 3,609
Self-citationThiebaut, F., Tsuruo, T., Hamada, H., Gottesman, M. M., Pastan, I., & Willingham, M. C. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.21.7735 · Cited by 2,777
Self-citationMechanisms of Cancer Drug Resistance
Gottesman, M. M. (2002) · Annual Review of Medicine · doi:10.1146/annurev.med.53.082901.103929 · Cited by 2,643
Self-citationSmit, J. J. M., Schinkel, A. H., Elferink, R. P. J. O., Groen, A. K., Wagenaar, E., van Deemter, L., Mol, C. A. A. M., Ottenhoff, R., van der Lugt, N. M. T., van Roon, M. A., et al. (1993) · Cell · doi:10.1016/0092-8674(93)90380-9 · Cited by 1,456
Metadata
- Authors
- Ueda, K., Cardarelli, C., Gottesman, M. M., & Pastan, I.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1987-05
- Volume
- 84
- Issue
- 9
- Pages
- 3004-3008
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2018652769
- Cited by
- 1,063
- References
- 0
- FWCI
- 17.31
- Type
- journal article
- Language
- en
- Open access
- green
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- Ueda, K., Cardarelli, C., Gottesman, M. M., & Pastan, I. (1987). Expression of a full-length cDNA for the human "MDR1" gene confers resistance to colchicine, doxorubicin, and vinblastine. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.84.9.3004
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