Isolation of the human anionic glutathione S-transferase cDNA and the relation of its gene expression to estrogen-receptor content in primary breast cancer

J. A. Moscow, A. J. Townsend, M. E. Goldsmith, J. Whang-Peng, P. J. Vickers, R. Poisson, S. Legault-Poisson, C. E. Myers, K. H. Cowan

Research output: Contribution to journalArticle

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Abstract

The development of multidrug resistance in MCF7 human breast cancer cells is associated with overexpression of P-glycoprotein, changes in activities of several detoxication enzymes, and loss of hormone sensitivity and estrogen receptors (ERs). We have cloned the cDNA for one of the drug-detoxifying enzymes overexpressed in multidrug-resistant MCF7 cells (Adr(R) MCF7) , the anionic isozyme of glutathione S-transferase (GSTπ). Hybridization with this GSTπ cDNA, GSTπ-1, demonstrated that increased GSTπ activity in Adr(R) MCF7 cells is associated with overexpression but not with amplification of the gene. We mapped the GSTπ gene to human chromosome 11q13 by in situ hybridization. Since multidrug resistance and GSTπ overexpression are associated with the loss of ERs in Adr(R) MCF7 cells, we examined several other breast cancer cell lines that were not selected for drug resistance. In each of these cell lines we found an inverse association between GSTπ expression and ER content. We also examined RNA from 21 primary breast cancers and found a similar association between GSTπ expression and ER content in vivo. GSTπ mRNA content in 11 ER-positive tumors (≤10 fmol/mg of protein) was significantly different from the GSTπ content of 10 ER-negative tumors (P = 0.002; Mann-Whitney Wilcoxon test for two independent samples). The finding of similar patterns of expression of a drug-detoxifying enzyme and of ERs in vitro as well as in vivo suggests that ER-negative breast cancer cells may have greater protection against antineoplastic agents conferred by GSTπ than ER-positive tumors.

Original languageEnglish
Pages (from-to)6518-6522
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume85
Issue number17
DOIs
Publication statusPublished - Jan 1 1988
Externally publishedYes

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Glutathione Transferase
Estrogen Receptors
Complementary DNA
Breast Neoplasms
Gene Expression
MCF-7 Cells
Multiple Drug Resistance
Enzymes
Cell Line
Neoplasms
Gene Amplification
Human Chromosomes
P-Glycoprotein
Drug Resistance
Pharmaceutical Preparations
Antineoplastic Agents
Isoenzymes
In Situ Hybridization
Hormones
RNA

ASJC Scopus subject areas

  • General

Cite this

Isolation of the human anionic glutathione S-transferase cDNA and the relation of its gene expression to estrogen-receptor content in primary breast cancer. / Moscow, J. A.; Townsend, A. J.; Goldsmith, M. E.; Whang-Peng, J.; Vickers, P. J.; Poisson, R.; Legault-Poisson, S.; Myers, C. E.; Cowan, K. H.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 85, No. 17, 01.01.1988, p. 6518-6522.

Research output: Contribution to journalArticle

Moscow, J. A. ; Townsend, A. J. ; Goldsmith, M. E. ; Whang-Peng, J. ; Vickers, P. J. ; Poisson, R. ; Legault-Poisson, S. ; Myers, C. E. ; Cowan, K. H. / Isolation of the human anionic glutathione S-transferase cDNA and the relation of its gene expression to estrogen-receptor content in primary breast cancer. In: Proceedings of the National Academy of Sciences of the United States of America. 1988 ; Vol. 85, No. 17. pp. 6518-6522.
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AU - Whang-Peng, J.

AU - Vickers, P. J.

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