Work

Cisplatin and Adriamycin Resistance Are Associated with MutLα and Mismatch Repair Deficiency in an Ovarian Tumor Cell Line

Year: 1996

Type: article

Abstract: 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.

Source: Journal of Biological Chemistry

DOI: 10.1074/jbc.271.33.19645

Authors: James T. Drummond, Alan Anthoney, Robert Brown, Paul Modrich

Institutions: Howard Hughes Medical Institute, Duke University, Duke Medical Center, Cancer Research UK Scotland Institute

Language: English

Topic: DNA Repair Mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,430