Expression of Anionic Glutathione-S-transferase and P-Glycoprotein Genes in Human Tissues and Tumors

Jeffrey A. Moscow, Craig R. Fairchild, Mary Jane Madden, David T. Ransom, Harry S. Wieand, Erin E. O'Brien, David G. Poplack, Jeffrey Cossman, Charles E. Myers, Kenneth H Cowan

Research output: Contribution to journalArticle

336 Citations (Scopus)

Abstract

The development of multidrug resistance in MCF-7 human breast cancer cells and the acquisition of broad resistance to xenobiotics in rat hyperplastic nodules are both associated with increased P-glycoprotein (mdr) gene expression as well as changes in activities of intracellular detoxication enzymes; among these changes is a significant increase in the activity of the anionic isozyme of glutathione-s-transferase (GST). We have isolated a cDNA encoding the human anionic glutathione-S-transferase, GSTπ-l, from a cDNA library constructed from multidrug-resistant MCF-7 cells. The deduced amino add sequence of GSTπ-1 shows that while the human anionic GST displays 85% nucleotide and amino acid sequence homology to the rat anionic isozyme, it is markedly less related to human basic GST isozymes. We have examined the expression of GST and P-glycoprotein in 170 specimens of human tissues and tumors. P-Glycoprotein RNA expression was positive in eight of 23 lymphomas and two of 12 colon tumors; however, many other normal and malignant tissues, including lung, bladder, and breast tumors, had low or undetectable levels of P-glycoprotein RNA expression. In contrast, GST was readily detected in a wide variety of normal and malignant tissues. The level of GSTπ mRNA expression in normal tissues was heterogeneous, with lowest levels found in liver and the highest levels found in lung, esophagus, and placenta. GSTπ was also variably expressed in human tumors, with the lowest relative levels occurring in lymphoma and breast cancer and the highest levels found in lung cancer and head and neck tumors. In addition, comparison of paired specimens from the same patient indicated that GSTπ expression was increased in many tumors relative to matched normal tissue.

Original languageEnglish (US)
Pages (from-to)1422-1428
Number of pages7
JournalCancer Research
Volume49
Issue number6
StatePublished - Mar 15 1989

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P-Glycoprotein
Glutathione Transferase
Genes
Neoplasms
Isoenzymes
Breast Neoplasms
Lymphoma
RNA
Matched-Pair Analysis
Amino Acid Sequence Homology
Lung
MCF-7 Cells
Multiple Drug Resistance
Xenobiotics
Head and Neck Neoplasms
Gene Library
Urinary Bladder Neoplasms
Placenta
Esophagus
Lung Neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Moscow, J. A., Fairchild, C. R., Madden, M. J., Ransom, D. T., Wieand, H. S., O'Brien, E. E., ... Cowan, K. H. (1989). Expression of Anionic Glutathione-S-transferase and P-Glycoprotein Genes in Human Tissues and Tumors. Cancer Research, 49(6), 1422-1428.

Expression of Anionic Glutathione-S-transferase and P-Glycoprotein Genes in Human Tissues and Tumors. / Moscow, Jeffrey A.; Fairchild, Craig R.; Madden, Mary Jane; Ransom, David T.; Wieand, Harry S.; O'Brien, Erin E.; Poplack, David G.; Cossman, Jeffrey; Myers, Charles E.; Cowan, Kenneth H.

In: Cancer Research, Vol. 49, No. 6, 15.03.1989, p. 1422-1428.

Research output: Contribution to journalArticle

Moscow, JA, Fairchild, CR, Madden, MJ, Ransom, DT, Wieand, HS, O'Brien, EE, Poplack, DG, Cossman, J, Myers, CE & Cowan, KH 1989, 'Expression of Anionic Glutathione-S-transferase and P-Glycoprotein Genes in Human Tissues and Tumors', Cancer Research, vol. 49, no. 6, pp. 1422-1428.
Moscow JA, Fairchild CR, Madden MJ, Ransom DT, Wieand HS, O'Brien EE et al. Expression of Anionic Glutathione-S-transferase and P-Glycoprotein Genes in Human Tissues and Tumors. Cancer Research. 1989 Mar 15;49(6):1422-1428.
Moscow, Jeffrey A. ; Fairchild, Craig R. ; Madden, Mary Jane ; Ransom, David T. ; Wieand, Harry S. ; O'Brien, Erin E. ; Poplack, David G. ; Cossman, Jeffrey ; Myers, Charles E. ; Cowan, Kenneth H. / Expression of Anionic Glutathione-S-transferase and P-Glycoprotein Genes in Human Tissues and Tumors. In: Cancer Research. 1989 ; Vol. 49, No. 6. pp. 1422-1428.
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abstract = "The development of multidrug resistance in MCF-7 human breast cancer cells and the acquisition of broad resistance to xenobiotics in rat hyperplastic nodules are both associated with increased P-glycoprotein (mdr) gene expression as well as changes in activities of intracellular detoxication enzymes; among these changes is a significant increase in the activity of the anionic isozyme of glutathione-s-transferase (GST). We have isolated a cDNA encoding the human anionic glutathione-S-transferase, GSTπ-l, from a cDNA library constructed from multidrug-resistant MCF-7 cells. The deduced amino add sequence of GSTπ-1 shows that while the human anionic GST displays 85{\%} nucleotide and amino acid sequence homology to the rat anionic isozyme, it is markedly less related to human basic GST isozymes. We have examined the expression of GST and P-glycoprotein in 170 specimens of human tissues and tumors. P-Glycoprotein RNA expression was positive in eight of 23 lymphomas and two of 12 colon tumors; however, many other normal and malignant tissues, including lung, bladder, and breast tumors, had low or undetectable levels of P-glycoprotein RNA expression. In contrast, GST was readily detected in a wide variety of normal and malignant tissues. The level of GSTπ mRNA expression in normal tissues was heterogeneous, with lowest levels found in liver and the highest levels found in lung, esophagus, and placenta. GSTπ was also variably expressed in human tumors, with the lowest relative levels occurring in lymphoma and breast cancer and the highest levels found in lung cancer and head and neck tumors. In addition, comparison of paired specimens from the same patient indicated that GSTπ expression was increased in many tumors relative to matched normal tissue.",
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