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

Publication ,  Journal Article
Drummond, JT; Anthoney, A; Brown, R; Modrich, P
Published in: J Biol Chem
August 16, 1996

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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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

August 16, 1996

Volume

271

Issue

33

Start / End Page

19645 / 19648

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Ovarian Neoplasms
  • Nuclear Proteins
  • Neoplasm Proteins
  • MutL Protein Homolog 1
  • Mismatch Repair Endonuclease PMS2
  • Humans
  • Female
  • Drug Resistance
  • Doxorubicin
 

Citation

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Drummond, J. T., Anthoney, A., Brown, R., & Modrich, P. (1996). Cisplatin and adriamycin resistance are associated with MutLalpha and mismatch repair deficiency in an ovarian tumor cell line. J Biol Chem, 271(33), 19645–19648. https://doi.org/10.1074/jbc.271.33.19645
Drummond, J. T., A. Anthoney, R. Brown, and P. Modrich. “Cisplatin and adriamycin resistance are associated with MutLalpha and mismatch repair deficiency in an ovarian tumor cell line.J Biol Chem 271, no. 33 (August 16, 1996): 19645–48. https://doi.org/10.1074/jbc.271.33.19645.
Drummond JT, Anthoney A, Brown R, Modrich P. Cisplatin and adriamycin resistance are associated with MutLalpha and mismatch repair deficiency in an ovarian tumor cell line. J Biol Chem. 1996 Aug 16;271(33):19645–8.
Drummond, J. T., et al. “Cisplatin and adriamycin resistance are associated with MutLalpha and mismatch repair deficiency in an ovarian tumor cell line.J Biol Chem, vol. 271, no. 33, Aug. 1996, pp. 19645–48. Pubmed, doi:10.1074/jbc.271.33.19645.
Drummond JT, Anthoney A, Brown R, Modrich P. Cisplatin and adriamycin resistance are associated with MutLalpha and mismatch repair deficiency in an ovarian tumor cell line. J Biol Chem. 1996 Aug 16;271(33):19645–19648.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

August 16, 1996

Volume

271

Issue

33

Start / End Page

19645 / 19648

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Ovarian Neoplasms
  • Nuclear Proteins
  • Neoplasm Proteins
  • MutL Protein Homolog 1
  • Mismatch Repair Endonuclease PMS2
  • Humans
  • Female
  • Drug Resistance
  • Doxorubicin