Overexpression of Metallothionein Confers Resistance to Anticancer Drugs

American Association for the Advancement of Science (AAAS) - Tập 241 Số 4874 - Trang 1813-1815 - 1988
Susan L. Kelley1, Alakananda Basu2, Beverly A. Teicher3, Miles P. Hacker4, Dean H. Hamer5, John S. Lazo2
1Pharmaceutical Research and Development Division, Bristol Myers Co., Wallingford, CIT 06492.
2Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261
3Department of Pathology, Harvard University, and Dana-Farber Cancer Center, Boston, MA 02115.
4Department of Pharmacology, University of Vermont, Burlington, VT 05401.
5Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.

Tóm tắt

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-II A 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.

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American Association for the Advancement of Science (AAAS)

Tập 241 Số 4874

1813-1815

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