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      Sphingosine kinase regulates hepatoma cell differentiation: roles of hepatocyte nuclear factor and retinoid receptor.

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          Abstract

          In hepatoma Huh-7 cells, inhibition of sphingosine kinase (SphK) activity by N,N-dimethylsphingosine (DMS) resulted in up-regulated production of liver-specific serum proteins including albumin and alpha-fetoprotein (AFP). The changes in these protein levels coincided well with those of two liver-enriched transcription factors, hepatocyte nuclear factor (HNF)-1 and -4, which regulate a number of liver-specific genes at the transcriptional level. Moreover, DMS induced the expression of retinoic acid receptor-alpha and retinoid X receptor-alpha. In DMS-treated cells, 9-cis retinoic acid (RA) further enhanced HNF-4alpha and albumin expression but it inhibited AFP accumulation. These results suggest that activation of SphK disengages cells from their liver-specific phenotype, and that 9-cis RA further induces differentiation of hepatoma cells when SphK activity is inhibited.

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          Author and article information

          Journal
          Biochem. Biophys. Res. Commun.
          Biochemical and biophysical research communications
          Elsevier BV
          0006-291X
          0006-291X
          Aug 31 2001
          : 286
          : 4
          Affiliations
          [1 ] First Department of Internal Medicine, Gifu University School of Medicine, Tsukasamachi-40, Gifu 500-8705, Japan.
          Article
          S0006-291X(01)95451-8
          10.1006/bbrc.2001.5451
          11520048
          64da962b-4c98-423d-8339-467a89fb821a
          History

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