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Expression of glutathione S-transferase P1-1 in leukemic cells is regulated by inducible AP-1 binding

Authors
Type
Published Article
Journal
Cancer Letters
0304-3835
Publisher
Elsevier
Volume
216
Issue
2
Pages
207–219
Identifiers
DOI: 10.1016/j.canlet.2004.05.004
Source
LBMCC
Keywords
  • Oncology
  • Leukemia
  • Cancer Research
  • Glutathione S-Transferase P1-1
  • Oxidative Stress
  • Activator Protein-1
  • Chemoresistance

Abstract

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.

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