title: Overexpression of metallothionein confers resistance to anticancer drugs.
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.
authors.affiliation: Pharmaceutical Research and Development Division, Bristol Myers Co., Wallingford, CT 06492.
authors.forename: S L
authors.initials: SL
authors.lastname: Kelley
authors.forename: A
authors.initials: A
authors.lastname: Basu
authors.forename: B A
authors.initials: BA
authors.lastname: Teicher
authors.forename: M P
authors.initials: MP
authors.lastname: Hacker
authors.forename: D H
authors.initials: DH
authors.lastname: Hamer
authors.forename: J S
authors.initials: JS
authors.lastname: Lazo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents; D015152:Blotting, Northern; D002478:Cells, Cultured; D004351:Drug Resistance; D066298:In Vitro Techniques; D008668:Metallothionein / Q000502:physiology*; D051379:Mice
chemical_list: D000970:Antineoplastic Agents; D008668:Metallothionein