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

doi:10.1126/science.3175622

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 journal › Article › peer-review

609 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-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.

Original language	English
Pages (from-to)	1813-1815
Number of pages	3
Journal	Science
Volume	241
Issue number	4874
DOIs	https://doi.org/10.1126/science.3175622
State	Published - 1988

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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.",

author = "Kelley, {Susan L.} and Alakananda Basu and Teicher, {Beverly A.} and Hacker, {Miles P.} and Hamer, {Dean H.} and Lazo, {John S.}",

year = "1988",

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volume = "241",

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T1 - Overexpression of metallothionein confers resistance to anticancer drugs

AU - Kelley, Susan L.

AU - Basu, Alakananda

AU - Teicher, Beverly A.

AU - Hacker, Miles P.

AU - Hamer, Dean H.

AU - Lazo, John S.

PY - 1988

Y1 - 1988

N2 - 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.

AB - 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.

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Overexpression of metallothionein confers resistance to anticancer drugs

Abstract

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