Inhibition of spermidine synthase gene expression by transforming growth factor-beta 1 in hepatoma cells.
Inhibition of spermidine synthase gene expression by transforming growth factor-beta 1 in hepatoma cells.
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通过转化生长因子-β1抑制肝癌细胞中亚精胺合酶基因的表达。
DOI：
10.1042/bj3210537
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Carr,BI
中科院分区：
文献类型：
--
作者：
Nishikawa,Y;Kar,S;Wiest,L;Pegg,AE;Carr,BI
We screened genes responsive to transforming growth factor-α (TGF-α1) protein in a human hepatoma cell line (Hep3B) using a PCR-mediated differential display technique, in order to investigate the mechanisms involved in TGF-α-induced growth suppression. We found a gene that was down-regulated by TGF-α1to 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-α1treatment of Hep3B cells. The inhibition of spermidine synthase gene expression by TGF-α1protein was also observed in other hepatoma cell lines. The expression of genes for other biosynthetic enzymes in polyamine metabolism (ornithine decarboxylase andS-adenosylmethionine decarboxylase) was also inhibited to the same extent as for spermidine synthase, while the gene expression of spermidine/spermineN1-acetyltransferase, a catabolic enzyme, was relatively resistant to TGF-α1. Spermine levels in Hep3B cells were decreased by TGF-α1treatment, although the levels of spermidine and putrescine were unchanged, probably due to compensation by remaining spermidine/spermineN1-acetyltransferase activity. Exogenously added spermidine or spermine, but not putrescine, partially antagonized the growth-inhibitory effects of TGF-α1on 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-α-induced growth suppression.
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影响因子：
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