Overexpression of Metallothionein Confers Resistance to Anticancer Drugs

• DOI: 10.1126/science.3175622
• Publication Date: 2006-10-05T21:21:15Z
• Authors: Susan L. Kelley; Alakananda Basu; Beverly A. Teicher; Miles P. Hacker; Dean H. Hamer; John S Lazo
• Keywords: Mice; 03 medical and health sciences; 0302 clinical medicine; Drug Resistance; Animals; Antineoplastic Agents; Metallothionein; In Vitro Techniques; Blotting, Northern; Cells, Cultured; 3. Good health

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.