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Expression of hepatocyte growth factor receptor (c-met) mRNA in primary cultures of human hepatocytes
  1. S Hirono,
  2. S Afford,
  3. A J Strain
  1. Liver Research Laboratories, Queen Elizabeth Hospital and School of Biochemistry, University of Birmingham, Edgbaston, Birmingham B15 2TH

    Abstract

    Aim—To investigate the regulation of hepatocyte growth factor (HGF) receptor (c-met) gene expression in isolated primary human hepatocytes.

    Methods—Primary hepatocytes were maintained in monolayer culture for up to 72 hours in serum-free medium. They were treated with growth factors and the level of HGF, c-met and reduced glyceraldehyde-phosphate dehydrogenase mRNA expression determined by northern blot analysis.

    Results—Hepatocytes expressed a single 9 kilobase c-met gene transcript whilst HGF mRNA analysis was negative. Addition of HGF and epidermal growth factor, both potent mitogens for human hepatocytes, enhanced c-met mRNA expression approximately twofold within 24 hours, after which levels returned to normal. In non-growth factor treated cells, transforming growth factor-β (TGFβ) had little effect upon c-met mRNA levels. However, TGFβ inhibited the HGF induced increase in c-met mRNA levels.

    Conclusions—These results indicate that hepatocytes which proliferate in response to HGF demonstrate levels of c-met mRNA which are subject to growth factor modulation and suggest an important means of growth regulatory control.

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