Overexpression of Metallothionein Confers Resistance to Anticancer Drugs
- 30 September 1988
- journal article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 241 (4874) , 1813-1815
- https://doi.org/10.1126/science.3175622
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.Keywords
This publication has 20 references indexed in Scilit:
- The formation, isolation and characterization of DNA adducts produced by anticancer platinum complexesPharmacology & Therapeutics, 1987
- METALLOTHIONEINAnnual Review of Biochemistry, 1986
- X-Ray Structure of the Major Adduct of the Anticancer Drug Cisplatin with DNA: cis -[Pt(NH 3 ) 2 {d(pGpG)}]Science, 1985
- Comparison of methods of metallothionein quantification: Cadmium radioassay, mercury radioassay, and radioimmunoassayToxicology and Applied Pharmacology, 1985
- Binding of cis-dichlorodiammine platinum(II) to metallothionein in Ehrlich cellsBiochemical and Biophysical Research Communications, 1985
- Metallothionein – A Unique Protein with Multiple Detoxifying Properties?European Surgical Research, 1984
- Zinc effects on glutathione metabolism relationship to zinc-induced protection from alkylating agentsBiochemical Pharmacology, 1983
- Resistance against cis-dichlorodiammineplatinum in cultured cells with a high content of metallothioneinToxicology and Applied Pharmacology, 1981
- Studies on the resistance of a murine leukemia L1210 cell line to cis-diamminedichloroplatinium(II)Biochemical Pharmacology, 1981
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976