SULF1/SULF2 reactivation during liver damage and tumour growth.

Both SULF1 and SULF2 enzymes are undetectable in normal adult liver tissue despite their high level expression during foetal development. Most hepatocellular carcinomas unlike the normal adult liver, however, express variable levels of these enzymes with a small proportion not expressing either SULF...

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Publicado en:Histochemistry & Cell Biology Vol. 146; no. 1; pp. 85 - 98
Autores principales: Graham, Kurtis, Murphy, Joshua, Dhoot, Gurtej
Formato: Journal Article
Publicado: Springer Nature Jul2016
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Jul2016
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      pub: Springer Nature
      place: New York, New York
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        116237244
        10.1007/s00418-016-1425-8
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        atl: SULF1/SULF2 reactivation during liver damage and tumour growth.
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          Graham, Kurtis
          Murphy, Joshua
          Dhoot, Gurtej
        affil: Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, London UK
      sug:
      ab: Both SULF1 and SULF2 enzymes are undetectable in normal adult liver tissue despite their high level expression during foetal development. Most hepatocellular carcinomas unlike the normal adult liver, however, express variable levels of these enzymes with a small proportion not expressing either SULF1 or SULF2. SULF1 expression, however, is not restricted to only foetal and tumour tissues but is also abundant in liver tissues undergoing injury-induced tissue regeneration as we observed during fatty liver degeneration, chronic hepatitis and cirrhosis. Unlike SULF1, the level of SULF2 activation during injury-induced regeneration, however, is much lower when compared to foetal or tumour growth. Although a small fraction of liver tumours and some liver tumour cell lines can grow in the absence of Sulf1 and/or Sulf2, the in vitro overexpression of these genes further confirms their growth-promoting effect while transient reduction in their levels by neutralisation antibodies reduces growth. Hedgehog signalling appeared to regulate the growth of both Hep3B and PRF5 cell lines since cyclopamine demonstrated a marked inhibitory effect while sonic hedgehog (SHH) overexpression promoted growth. All Sulf isoforms promoted SHH-induced growth although the level of increase in PRF5 cell line was higher with both Sulf2 variants than Sulf1. In addition to promoting growth, the Sulf variants, particularly the shorter Sulf2 variant, markedly promoted PRF5 cell migration in a scratch assay. The SULF1/SULF2 activation thus does not only promote regulated foetal growth and injury-induced liver regeneration but also dysregulated tumour growth.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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