Inhibition of spermidine synthase gene expression by transforming growth factor-β1 in hepatoma cells

Y. Nishikawa, S. Kar, L. Wiest, A. E. Pegg, B. I. Carr

Research output: Contribution to journalArticle

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Abstract

We screened genes responsive to transforming growth factor-β (TGF-β1) protein in a human hepatoma cell line (Hep3B) using a PCR-mediated differential display, technique, in order to investigate the mechanisms involved in TGF-β-induced growth suppression. We found a gene that was down-regulated by TGF-β1 to be completely identical in an approx. 620 bp segment to the gene for the enzyme spermidine synthase, which mediates the conversion of putrescine into spermidine. Both spermidine synthase mRNA expression and its enzyme activity were decreased after TGF-β1 treatment of Hep3B cells. The inhibition of spermidine synthase gene expression by TGF-β1, protein was also observed in other hepatoma cell lines. The expression of genes for other biosynthetic enzymes in polyamine metabolism (ornithine decarboxylase and S-adenosylmethionine decarboxylase) was also inhibited to the same extent as for spermidine synthase, while the gene expression of spermidine/spermine N1-acetyltransferase, a catabolic enzyme, was relatively resistant to TGF-β1. Spermine levels in Hep3B cells were decreased by TGF-β1 treatment, although the levels of spermidine and putrescine were unchanged, probably due to compensation by remaining spermidine/spermine N1-acetyltransferase activity. Exogenously added spermidine or spermine, but not putrescine, partially antagonized the growth-inhibitory effects of TGF-β1, on Hep3B cells. Our data suggest that down-regulation of gene expression of the enzymes involved in polyamine metabolism, including spermidine synthase, may be associated with the mechanism of TGF-β-induced growth suppression.

Original languageEnglish (US)
Pages (from-to)537-543
Number of pages7
JournalBiochemical Journal
Volume321
Issue number2
DOIs
StatePublished - Jan 1 1997

Fingerprint

Spermidine Synthase
Spermidine
Transforming Growth Factors
Gene expression
Spermine
Hepatocellular Carcinoma
Putrescine
Gene Expression
Genes
Enzymes
Acetyltransferases
Polyamines
Metabolism
Growth
Adenosylmethionine Decarboxylase
Cells
Cell Line
Ornithine Decarboxylase
Gene Expression Regulation
Enzyme activity

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Nishikawa, Y. ; Kar, S. ; Wiest, L. ; Pegg, A. E. ; Carr, B. I. / Inhibition of spermidine synthase gene expression by transforming growth factor-β1 in hepatoma cells. In: Biochemical Journal. 1997 ; Vol. 321, No. 2. pp. 537-543.
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Inhibition of spermidine synthase gene expression by transforming growth factor-β1 in hepatoma cells. / Nishikawa, Y.; Kar, S.; Wiest, L.; Pegg, A. E.; Carr, B. I.

In: Biochemical Journal, Vol. 321, No. 2, 01.01.1997, p. 537-543.

Research output: Contribution to journalArticle

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