Differential expression of methionine adenosyltransferase genes influences the rate of growth of human hepatocellular carcinoma cells.
Differential expression of methionine adenosyltransferase genes influences the rate of growth of human hepatocellular carcinoma cells.
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发表时间：
1998-04
期刊：
影响因子：
11.2
通讯作者：
Jiaxin Cai;Z. Mao;J. Hwang;Shelly C. Lu
中科院分区：
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作者：
Jiaxin Cai;Z. Mao;J. Hwang;Shelly C. Lu
甲硫氨酸腺苷转移酶（MAT）催化S-腺苷甲硫氨酸（SAM）的形成，SAM是主要的甲基供体，对正常细胞功能至关重要。MAT的两种形式，肝特异性和非肝特异性，分别是两个基因MAT 1A和MAT 2A的产物。我们已经报道了在人肝癌细胞中从MAT 1A到MAT 2A基因表达的转换。在目前的工作中，我们研究了细胞表达的MAT类型是否影响细胞生长。用MAT 1A稳定转染HuH-7细胞，随后用针对MAT 2A的反义寡核苷酸处理。MAT 2A反义处理使MAT 2A mRNA的量减少99%，但对MAT 1A mRNA没有影响。细胞生长和DNA合成速率在用MAT 1A转染后降低约20-25%，并且在MAT 2A反义处理后降低另外30-40%。SAM水平和SAM：S-腺苷高半胱氨酸（SAH）比率在MAT 1A转染后增加50-75%，并且在MAT 2A反义处理后额外增加60-80%。DNA甲基化的变化与SAM水平和SAM：SAH比率的变化平行。在培养基中补充SAM的未转染的HuH-7细胞增加SAM水平、SAM：SAH比率和DNA甲基化，并降低细胞生长和DNA合成。总之，细胞生长受到表达的MAT类型的影响。其机制可能涉及SAM：SAH比例和DNA甲基化的变化。
Methionine adenosyltransferase (MAT) catalyzes the formation of S-adenosylmethionine (SAM), the principal methyl donor, and is essential to normal cell function. The two forms of MAT, liver specific and non-liver specific, are products of two genes, MAT1A and MAT2A, respectively. We have reported a switch from MAT1A to MAT2A gene expression in human liver cancer cells. In the current work, we examined whether the type of MAT expressed by the cell influences cell growth. HuH-7 cells were stably transfected with MAT1A and were subsequently treated with antisense oligonucleotides directed against MAT2A. MAT2A antisense treatment reduced the amount of MAT2A mRNA by 99% but had no effect on MAT1A mRNA. Cell growth and DNA synthesis rates were reduced by approximately 20-25% after transfection with MAT1A and by an additional 30-40% after MAT2A antisense treatment. SAM level and SAM:S-adenosylhomocysteine (SAH) ratio increased by 50-75% after MAT1A transfection and by an additional 60-80% after MAT2A antisense treatment. DNA methylation changed in parallel to changes in SAM level and SAM:SAH ratio. Supplementing untransfected HuH-7 cells with SAM in the culture medium increased SAM level, SAM:SAH ratio, and DNA methylation and decreased cell growth and DNA synthesis. In conclusion, cell growth is influenced by the type of MAT expressed. The mechanism likely involves changes in SAM:SAH ratio and DNA methylation.