| Expression of glutathione S-transferase P1-1 in leukemic cells is regulated by inducible AP-1 binding. | |
MedLine Citation:
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PMID: 15533597 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
Authors:
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Annelyse Duvoix; Michaël Schnekenburger; Sylvie Delhalle; Romain Blasius; Patricia Borde-Chiché; Franck Morceau; Mario Dicato; Marc Diederich |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cancer letters Volume: 216 ISSN: 0304-3835 ISO Abbreviation: Cancer Lett. Publication Date: 2004 Dec |
Date Detail:
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Created Date: 2004-11-09 Completed Date: 2005-02-18 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 7600053 Medline TA: Cancer Lett Country: Ireland |
Other Details:
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Languages: eng Pagination: 207-19 Citation Subset: IM |
Affiliation:
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Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, 9, rue Edward Steichen, L-2540 Luxembourg, Luxembourg. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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 Humans Hydrogen Peroxide / pharmacology Hydroquinones / pharmacology Isoenzymes / biosynthesis*, genetics Jurkat Cells K562 Cells Leukemia Mutagenesis, Site-Directed Promoter Regions, Genetic Tetradecanoylphorbol Acetate / pharmacology Transcription Factor AP-1 / biosynthesis, genetics, metabolism* Transcription, Genetic Transfection U937 Cells |
| Chemical | |
Reg. No./Substance:
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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 2.5.1.18/GSTP1 protein, human; EC 2.5.1.18/Glutathione S-Transferase pi; EC 2.5.1.18/Glutathione Transferase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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