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Blood, 1 July 2005, Vol. 106, No. 1, pp. 304-310. Prepublished online as a Blood First Edition Paper on March 10, 2005; DOI 10.1182/blood-2005-01-0241. This Article Full Text (PDF) Supplemental Table All Versions of this Article: 2005-01-0241v1 106/1/304    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Chou, W.-C. Articles by Dang, C. V Search for Related Content PubMed PubMed Citation Articles by Chou, W.-C. Articles by Dang, C. V Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 19, 2005 Accepted February 27, 2005 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, and Chi V Dang* Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; Program of Human Genetics and Molecular Biology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA Graduate Institute of Epidemiology, National Taiwan University, Taipei, Taiwan Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan Kimmel Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD, USA Program of Human Genetics and Molecular Biology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Kimmel Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Medicine, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA * Corresponding author; email: cvdang{at}jhmi.edu. The mechanism by which arsenic dramatically affects gene expression remains poorly understood. Here we report that prolonged exposure of the acute promyelocytic leukemia cells NB4 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 respond to both arsenic and hydrogen peroxide, but whose response to arsenic was reversed by an ROS scavenger, N-acetylcysteine. We find that 26% of the genes significantly responsive to arsenic may be 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 three genes, hTERT, C17 and c-Myc, whose expressions were significantly suppressed. We conclude that ROS contribute partly to arsenic-mediated gene regulation and Sp1 oxidation contributes to gene suppression by arsenic-induced ROS. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G.-M. Zou and A. Maitra Small-molecule inhibitor of the AP endonuclease 1/REF-1 E3330 inhibits pancreatic cancer cell growth and migration Mol. Cancer Ther., July 1, 2008; 7(7): 2012 - 2021. [Abstract] [Full Text] [PDF] T. Mijatovic, N. De Neve, P. Gailly, V. Mathieu, B. Haibe-Kains, G. Bontempi, J. Lapeira, C. Decaestecker, V. Facchini, and R. Kiss Nucleolus and c-Myc: potential targets of cardenolide-mediated antitumor activity Mol. Cancer Ther., May 1, 2008; 7(5): 1285 - 1296. [Abstract] [Full Text] [PDF] Z.-Y. Wang and Z. Chen Acute promyelocytic leukemia: from highly fatal to highly curable Blood, March 1, 2008; 111(5): 2505 - 2515. [Abstract] [Full Text] [PDF] S. H. Lam, C. L. Winata, Y. Tong, S. Korzh, W. S. Lim, V. Korzh, J. Spitsbergen, S. Mathavan, L. D. Miller, E. T. Liu, et al. Transcriptome kinetics of arsenic-induced adaptive response in zebrafish liver Physiol Genomics, November 21, 2006; 27(3): 351 - 361. [Abstract] [Full Text] [PDF] M. Argos, M. G. Kibriya, F. Parvez, F. Jasmine, M. Rakibuz-Zaman, and H. Ahsan Gene expression profiles in peripheral lymphocytes by arsenic exposure and skin lesion status in a bangladeshi population. Cancer Epidemiol. Biomarkers Prev., July 1, 2006; 15(7): 1367 - 1375. [Abstract] [Full Text] [PDF]

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