EXPRESSION OF GLUTATHIONE TRANSFERASE-PI IN BENIGN AND MALIGNANT LESIONS OF THE MELANOCYTE LINEAGE

被引:7
作者
NATALI, PG
NICOTRA, MR
CITRO, G
CUCCO, C
BIGOTTI, A
KANTOR, RRS
机构
[1] Regina Elena Cancer Institute, Rome
[2] Lab Immunology, Rome, 156, 00158, Via delle Messi D’Oro
[3] Institute for Biomedical Technology, CNR, Rome
[4] Department of Technology Development, National Cancer Institute, Frederick, MD
关键词
GLUTATHIONE-S-TRANSFERASE-PI; MELANOCYTE;
D O I
10.1097/00008390-199211000-00001
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Intrinsic and acquired resistance to chemotherapeutic agents represents the major clinical obstacle in the control of most tumours. In vitro studies have established that multiple mechanisms, including changes in drug uptake and efflux and in detoxifying enzymes, are responsible for drug resistance. Among the latter, glutathione S transferases (GST) have been recognized to play a relevant role. In the present study we have evaluated GSTpi immunohistochemically as well as enzymatically in benign and malignant primary and metastatic lesions of the melanocyte lineage. A parallel analysis of the multiple drug resistance (MDRI) gene product was performed in a representative number of specimens. Results of this study demonstrate that while GSTpi is constitutively expressed by the melanocyte lineage, independently from the transformed stage, MDRI p-glycoprotein is detected with a significantly lower frequency. These findings clearly indicate that GSTpi represents the major detoxifying metabolic pathway of the melanocyte lineage and may be responsible for the high degree of inherent resistance of malignant melanoma to available cytostatic treatments.
引用
收藏
页码:219 / 223
页数:5
相关论文
共 26 条
[1]  
Waxman D.J., Glutathione S-transferases: Role in alkylating agent resistance and possible target for modulation chemotherapy. A review, Cancer Res, 50, pp. 6449-6454, (1990)
[2]  
Van Der Blick A.M., Borst P., Multidrug resistance, Adv Cancer Res, 52, pp. 165-203, (1989)
[3]  
Kantor R.S., Giardina S.L., Bartolazzi A., Et al., Monoclonal antibodies to glutathione S-transferase π: Immunohistochemical analysis of human tissues and cancers, Int J Cancer, 47, pp. 193-201, (1991)
[4]  
Habig W.H., Jacoby W.B., Assay for differentiation of glutiathione S-transferase, Methods Enzymol, 77, pp. 398-405, (1981)
[5]  
Tietze F., Enzymic method for quantitative determina-tion of nanogram amounts of total and oxidized glutathione: Application to mammalian blood and other tissues, Anal Biochem, 27, pp. 502-522, (1965)
[6]  
Nistico P., Tecce R., Giacomini P., Et al., Effect of recombinant human leukocyte, fibroblast, and immune interferons on expression of class I and II major histocompatibility complex and invariant chain in early passage human melanoma cells, Cancer Res, 50, pp. 7422-7429, (1990)
[7]  
Natali P.G., Imai K., Wilson B.S., Et al., Structural properties and tissue distribution of the antigen recognized by the monoclonal antibody 653–405 to human melanoma cells, J Natl Cancer Inst, 67, pp. 591-601, (1981)
[8]  
Cenciarelli C., Currier S.J., Willingham M.C., Et al., Characterization by somatic cell genetics of a monoclonal antibody to the MDRI gene product (P-glycoprotein): Determination of p-glycoprotein expression in multidrug-resistant KB and CEM cell variants, Int J Cancer, 47, pp. 533-543, (1991)
[9]  
Tong W.A., Lee J., Wang R.M., Et al., Elimination of chemoresistant multiple myeloma clonogenic colony-forming cells by combined treatment with a plasma cell-reactive monoclonal antibody and a p-glycoprotein-reactive monoclonal antibody, Cancer Res, 49, pp. 4829-4834, (1989)
[10]  
Avrameas S., Ternynck T., The cross-linking of proteins with glutaraldehyde and its use for the preparation of immunoabsorbents, Immunochemistry, 6, pp. 53-66, (1969)