Cisplatin and adriamycin resistance are associated with MutLalpha and mismatch repair deficiency in an ovarian tumor cell line.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Drummond, JT; Anthoney, A; Brown, R; Modrich, P

Published Date

  • August 16, 1996

Published In

Volume / Issue

  • 271 / 33

Start / End Page

  • 19645 - 19648

PubMed ID

  • 8702663

Pubmed Central ID

  • 8702663

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.271.33.19645

Language

  • eng

Conference Location

  • United States