Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation

Wen Chien Chou, Hsuan Yu Chen, Sung Liang Yu, Linzhao Cheng, Pan Chyr Yang, Chi V. Dang

Research output: Contribution to journalArticle

Abstract

The mechanism by which arsenic dramatically affects gene expression remains poorly understood. Here we report that prolonged exposure of acute promyelocytic leukemia NB4 cells to low levels of arsenic trioxide increased the expression of a set of genes responsible for reactive oxygen species (ROS) production. We hypothesize that arsenic-induced ROS in turn contribute partially to altered gene expression. To identify genes responsive to arsenic-induced ROS, we used microarray gene expression analysis and identified genes that responded to arsenic and hydrogen peroxide but whose response to arsenic was reversed by an ROS scavenger, N-acetyl-L-cysteine. We found that 26% of the genes significantly responsive to arsenic might have been directly altered by ROS. We further explored the mechanisms by which ROS affects gene regulation and found that the Sp1 transcription factor was oxidized by arsenic treatment, with a corresponding decrease in its in situ binding on the promoters of 3 genes, hTERT, C17, and c-Myc, whose expressions were significantly suppressed. We conclude that ROS contributed partly to arsenic-mediated gene regulation and that Sp1 oxidation contributed to gene suppression by arsenic-induced ROS.

Original languageEnglish (US)
Pages (from-to)304-310
Number of pages7
JournalBlood
Volume106
Issue number1
DOIs
StatePublished - Jul 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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