FEBS Letters
Volume 582, Issue 13 , Pages 1859-1864, 11 June 2008

Transcriptional regulation of the hepatocyte growth factor gene by pyrrolidine dithiocarbamate

Edited by Beat Imhof

  • Phillip M. Harrison

      Affiliations

    • Kings College London, Department of Liver Studies and Transplantation, Denmark Hill Campus, Bessemer Road, London SE5 9RS, UK
    • Corresponding Author InformationCorresponding author. Fax: +44 (0) 20 3299 3167.
    • ,
  • Farzin Farzaneh

      Affiliations

    • Kings College London, Department of Haematological Medicine, The Rayne Institute, 123 Coldharbour Lane, London SE5 9NU, UK

Received 15 March 2008; received in revised form 29 April 2008; accepted 30 April 2008. published online 12 May 2008.

Abstract 

Hepatocyte growth factor (HGF) mediates cancer cell invasion and metastasis. This study characterised the down-regulation of HGF expression by pyrrolidine dithiocarbamate (PDTC), which markedly reduced HGF mRNA expression and protein production in MRC-5 cells. Reporter gene studies revealed that PDTC inhibited HGF gene transcription and that the response element is located in the region −75 to +42bp flanking the transcription initiation site. Electrophoretic mobility shift assay identified three specific protein complexes binding in this region, which were abrogated by exposure of cells to PDTC. PDTC deserves further investigation as a novel therapeutic agent for HGF-driven cancers.

Abbreviations: HGF, hepatocyte growth factor, PDTC, pyrrolidine dithiocarbamate, FCS, foetal calf serum, BS, bovine serum, PMA, phorbol 12-myristate 13-acetate, CAT, chloramphenicol acetyl transferase, EMSA, electrophoretic mobility shift assay, IL-1β, interleukin 1 beta, NAC, N-acetylcysteine

Keywords: Hepatocyte growth factor, Scatter factor, Pyrrolidine dithiocarbamate, Transcription factor, RNA stability

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PII: S0014-5793(08)00393-1

doi:10.1016/j.febslet.2008.04.055

FEBS Letters
Volume 582, Issue 13 , Pages 1859-1864, 11 June 2008

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