Overexpression of a novel anionic glutathione transferase in multidrug-resistent human breast cancer cells

G. Batist, A. Tulpule, B. K. Sinha, A. G. Katki, C. E. Myers, K. H. Cowan

Research output: Contribution to journalArticle

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Abstract

Adriamycin-resistant (Adr(R)) human breast cancer cells have been selected which exhibit cross-resistance to a wide range of anti-cancer drugs. This multidrug-resistant phenotype is associated with increases in the activities of glutathione peroxidase and glutathione transferase. The 45-fold increase in glutathione transferase activity is associated with the appearance of a new anionic isozyme in Adr(R) cells which is immunologically related to the anionic glutathione transferase present in human placenta. The increase in transferase and the level of drug resistance is relatively stable during passage of Adr(R) cells in the absence of adriamycin for over 10 months. A similar anionic glutathione transferase isozyme is also found in rat hyperplastic liver nodules, a preneoplastic state resulting from exposure to carcinogens. A rat cDNA which codes for the anionic glutathione transferase in rat hyperplastic nodules hybridizes to a 1.1-kilobase pair mRNA which is overexpressed in the Adr(R) MCF-7 cells. The anionic transferase has been purified from the Adr(R) cells and found to have characteristics which distinguish it from other anionic human glutathione transferases, including high levels of intrinsic peroxidase activity. The overexpression of a similar anionic glutathione transferase in human breast cancer cells selected for multidrug resistance and in rat hyperplastic liver nodules, which develop resistance to various hepatotoxins, suggests a possible role for this drug-conjugating enzyme in the mechanism of resistance in both of these states.

Original languageEnglish (US)
Pages (from-to)15544-15549
Number of pages6
JournalJournal of Biological Chemistry
Volume261
Issue number33
StatePublished - Dec 1 1986

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Glutathione Transferase
Cells
Breast Neoplasms
Rats
Transferases
Liver
Doxorubicin
Isoenzymes
Pharmaceutical Preparations
MCF-7 Cells
Multiple Drug Resistance
Glutathione Peroxidase
Drug Resistance
Carcinogens
Placenta
Peroxidase
Complementary DNA
Phenotype
Messenger RNA
Enzymes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Overexpression of a novel anionic glutathione transferase in multidrug-resistent human breast cancer cells. / Batist, G.; Tulpule, A.; Sinha, B. K.; Katki, A. G.; Myers, C. E.; Cowan, K. H.

In: Journal of Biological Chemistry, Vol. 261, No. 33, 01.12.1986, p. 15544-15549.

Research output: Contribution to journalArticle

Batist, G, Tulpule, A, Sinha, BK, Katki, AG, Myers, CE & Cowan, KH 1986, 'Overexpression of a novel anionic glutathione transferase in multidrug-resistent human breast cancer cells', Journal of Biological Chemistry, vol. 261, no. 33, pp. 15544-15549.
Batist, G. ; Tulpule, A. ; Sinha, B. K. ; Katki, A. G. ; Myers, C. E. ; Cowan, K. H. / Overexpression of a novel anionic glutathione transferase in multidrug-resistent human breast cancer cells. In: Journal of Biological Chemistry. 1986 ; Vol. 261, No. 33. pp. 15544-15549.
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