Overexpression of metallothionein confers resistance to anticancer drugs

Susan L. Kelley, Alakananda Basu, Beverly A. Teicher, Miles P. Hacker, Dean H. Hamer, John S. Lazo

Research output: Contribution to journalArticlepeer-review

597 Scopus citations

Abstract

Resistance to antineoplastic agents is the major obstacle to curative therapy of cancer. Tumor cell lines with acquired resistance to the antineoplastic agent cis-diamminedichloroplatinum(II) overexpressed metallothionein and demonstrated cross-resistance to alkylating agents such as chlorambucil and melphalan. Human carcinoma cells that maintained high levels of metallothionein because of chronic exposure to heavy metals were resistant to cis-diamminedichloroplatinum(II), melphalan, and chlorambucil. Furthermore, cells transfected with bovine papilloma virus expression vectors containing DNA encoding human metallothionein-IIA were resistant to cis-diamminedichloroplatinum(II), melphalan, and chlorambucil but not to 5-fluorouracil or vincristine. Thus, overexpression of metallothionein represents one mechanism of resistance to a subset of clinically important anticancer drugs.

Original languageEnglish
Pages (from-to)1813-1815
Number of pages3
JournalScience
Volume241
Issue number4874
DOIs
StatePublished - 1988

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