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Cisplatin and Adriamycin Resistance Are Associated with MutLα and Mismatch Repair Deficiency in an Ovarian Tumor Cell Line
Open accessAbstract
In contrast to parental A2780 ovarian tumor cells, extracts of one doxorubicin-resistant and two independent cis-diamminedichloroplatinum(II)-resistant derivatives are defective in strand-specific mismatch repair. The repair defect of the three hypermutable, drug-resistant cell lines is only evident when the strand break that directs the reaction is located 3' to the mismatch, and in each case repair is restored to extracts by addition of purified MutLalpha heterodimer. As judged by immunological assay, drug resistance is associated with the virtual absence of the MutLalpha MLH1 subunit and greatly reduced levels of the PMS2 subunit. These findings implicate a functional mismatch repair system in the cytotoxic effects of these antitumor drugs and may have ramifications for their clinical application.
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Citations
Cited by
Cellular processing of platinum anticancer drugs
Wang, D., & Lippard, S. J. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1691 · Cited by 3,801
Cisplatin: mode of cytotoxic action and molecular basis of resistance
Siddik, Z. H. (2003) · Oncogene · doi:10.1038/sj.onc.1206933 · Cited by 3,335
Molecular mechanisms of cisplatin resistance
Galluzzi, L., Senovilla, L., Vitale, I., Michels, J., Martins, I., Kepp, O., Castedo, M., & Kroemer, G. (2012) · Oncogene · doi:10.1038/onc.2011.384 · Cited by 2,760
Systems biology of cisplatin resistance: past, present and future
Galluzzi, L., Vitale, I., Michels, J., Brenner, C., Szabadkai, G., Harel-Bellan, A., Castedo, M., & Kroemer, G. (2014) · Cell Death & Disease · doi:10.1038/cddis.2013.428 · Cited by 782
Mismatch repair and DNA damage signalling
Stojic, L., Brun, R., & Jiricny, J. (2004) · DNA Repair · doi:10.1016/j.dnarep.2004.06.006 · Cited by 396
Metadata
- Authors
- Drummond, J. T., Anthoney, A., Brown, R., & Modrich, P.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1996-08
- Volume
- 271
- Issue
- 33
- Pages
- 19645-19648
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1982640212
- Cited by
- 295
- References
- 0
- FWCI
- 9.03
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: Cisplatin and Adriamycin Resistance Are Associated with MutLα and Mismatch Repair Deficiency in an Ovarian Tumor Cell Line. https://app.cochat.ai/papers/10.1074/jbc.271.33.19645
- The paper
- Drummond, J. T., Anthoney, A., Brown, R., & Modrich, P. (1996). Cisplatin and Adriamycin Resistance Are Associated with MutLα and Mismatch Repair Deficiency in an Ovarian Tumor Cell Line. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.271.33.19645
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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