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

Journal Article · Thu Sep 01 00:00:00 EDT 1988 · Proc. Natl. Acad. Sci. USA; (United States)

DOI:https://doi.org/10.1073/pnas.85.17.6518· OSTI ID:5821958

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

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). The authors have cloned the cDNA for one of the drug-detoxifying enzymes overexpressed in multidrug-resistant MCF7 cells (Adr/sup R/ MCF7), the anionic isozyme of glutathione S-transferase (GST/pi/). Hybridization with this GST/pi/ cDNA, GST/pi/-1, demonstrated that increased GST/pi/ activity in Adr/sup R/ MCF7 cells is associated with overexpression but not with amplification of the gene. They mapped the GST/pi/ gene to human chromosome 11q13 by in situ hybridization. Since multidrug resistance and GST/pi/ overexpression are associated with the loss of ERs in Adr/sup R/ MCF7 cells, they examined several other breast cancer cell lines that were not selected for drug resistance. In each of these cell lines they found an inverse association between GST/pi/ expression and ER content. They also examined RNA from 21 primary breast cancers and found a similar association between GST/pi/ expression and ER content in vivo. 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 GST/pi/ than ER-positive tumors.

• Research Organization: National Cancer Institute, Bethesda, MD (USA)
• OSTI ID: 5821958
• Journal Information: Proc. Natl. Acad. Sci. USA; (United States), Vol. 85:17
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ANTINEOPLASTIC DRUGS
TOXICITY
RECOMBINANT DNA
HYBRIDIZATION
TRANSFERASES
GENE REGULATION
ESTROGENS
GLUCOPROTEINS
HETEROCHROMOSOMES
LYMPHOCYTES
MAMMARY GLANDS
PHOSPHORUS 32
RECEPTORS
TRITIUM COMPOUNDS
TUMOR CELLS
ANIMAL CELLS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CARBOHYDRATES
CHROMOSOMES
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DNA
DRUGS
ENZYMES
GLANDS
GLYCOPROTEINS
HORMONES
ISOTOPES
LABELLED COMPOUNDS
LEUKOCYTES
LIGHT NUCLEI
MATERIALS
MEMBRANE PROTEINS
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PHOSPHORUS ISOTOPES
PROTEINS
RADIOISOTOPES
SACCHARIDES
SOMATIC CELLS
STEROID HORMONES
550201* - Biochemistry- Tracer Techniques