Document Detail

Expression of glutathione S-transferase P1-1 in leukemic cells is regulated by inducible AP-1 binding.
MedLine Citation:
PMID:  15533597     Owner:  NLM     Status:  MEDLINE    
Glutathione S-transferases (GST) are involved in cellular protection against xenobiotics, oxidative stress as well as in resistance against chemotherapeutic compounds such as doxorubicin. Levels of human placental type GSTP1-1 are known to be increased in many tumors and hematopoietic diseases. In this work, we compare transcriptional mechanisms in cells that express or not GSTP1-1. Transient transfection assays are used to show that different GST-promoter reporter constructs generate cell-type specific levels of luciferase activity. In expressing cells, transcriptional activity is strongly dependent on AP-1 binding elements within the -65 to -75 bp region of the GSTP1 gene as shown by site-directed mutagenesis. Electrophoretic mobility shift assays show that DNA binding activity is exclusively observed in GSTP1-1-expressing cells and is increased after stimulation with hydrogen peroxide, TPA, tert-butylhydroquinone and doxorubicin. Non-expressing cells present neither constitutive nor inducible AP-1 binding. Taken together, our results provide evidence for the induction of the GSTP1 gene via AP-1 binding activity in leukemia cells and contribute to a better understanding of the molecular events regulating genes involved in drug resistance mechanisms.
Annelyse Duvoix; Michaël Schnekenburger; Sylvie Delhalle; Romain Blasius; Patricia Borde-Chiché; Franck Morceau; Mario Dicato; Marc Diederich
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer letters     Volume:  216     ISSN:  0304-3835     ISO Abbreviation:  Cancer Lett.     Publication Date:  2004 Dec 
Date Detail:
Created Date:  2004-11-09     Completed Date:  2005-02-18     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  207-19     Citation Subset:  IM    
Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, 9, rue Edward Steichen, L-2540 Luxembourg, Luxembourg.
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MeSH Terms
Binding Sites
Doxorubicin / pharmacology
Electrophoretic Mobility Shift Assay
Gene Expression Regulation, Enzymologic* / drug effects
Gene Expression Regulation, Neoplastic* / drug effects
Glutathione S-Transferase pi
Glutathione Transferase / biosynthesis*,  genetics
Hydrogen Peroxide / pharmacology
Hydroquinones / pharmacology
Isoenzymes / biosynthesis*,  genetics
Jurkat Cells
K562 Cells
Mutagenesis, Site-Directed
Promoter Regions, Genetic
Tetradecanoylphorbol Acetate / pharmacology
Transcription Factor AP-1 / biosynthesis,  genetics,  metabolism*
Transcription, Genetic
U937 Cells
Reg. No./Substance:
0/Hydroquinones; 0/Isoenzymes; 0/Transcription Factor AP-1; 16561-29-8/Tetradecanoylphorbol Acetate; 1948-33-0/2-tert-butylhydroquinone; 23214-92-8/Doxorubicin; 7722-84-1/Hydrogen Peroxide; EC protein, human; EC S-Transferase pi; EC Transferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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