[Regulation of human β-1,4-galactosyltransferase V gene expression in cancer cells].
[Regulation of human β-1,4-galactosyltransferase V gene expression in cancer cells].
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人β-1,4-半乳糖基转移酶V基因在癌细胞中的表达调控[J].
DOI：
10.1248/yakushi.132.691
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
K. Furukawa
中科院分区：
文献类型：
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作者：
Takeshi Sato;K. Furukawa
β-1，4-半乳糖基转移酶(β-1，4-GalT)V是我们克隆的人和小鼠基因，体外研究表明它与N-聚糖、O-多糖和乳糖神经酰胺的生物合成有关。我们最近的研究表明，β-1，4-GalT V基因敲除小鼠具有胚胎致死性，提示β-1，4-GalT V合成的多糖对胚胎发育具有重要意义。随后的研究表明，小鼠β-1，4-GalT V参与了乳糖基神经酰胺的生物合成。众所周知，当细胞发生恶性转化时，细胞表面糖蛋白和糖脂的糖基化会发生显着变化。我们发现，在6个β-1，4-GalT中，只有β-1，4-GalT V的基因在恶性转化过程中表达增加。β-1，4-GalT V基因在癌细胞中的表达受转录因子Sp1和Ets-1的调控。这两种转录因子不仅调节糖基转移酶的基因表达水平，而且还调节与肿瘤生长、侵袭和转移有关的关键分子的表达。因此，肿瘤细胞的异常糖基化和恶性表型被认为是通过调节转录因子基因的表达水平而被抑制的。本文综述了β-1，4-GalT V的基因发现、体内功能和转录机制，并对转录因子基因的调控在肿瘤治疗中的应用进行了展望。
β-1,4-Galactosyltransferase (β-1,4-GalT) V - whose human and mouse genes were cloned by us - has been suggested to be involved in the biosyntheses of N-glycans, O-glycans, and lactosylceramide by in vitro studies. Our recent study showed that β-1,4-GalT V-knockout mice are embryonic lethal, suggesting the importance of the glycans synthesized by β-1,4-GalT V for embryonic development. A subsequent study showed that murine β-1,4-GalT V is involved in the biosynthesis of lactosylceramide. It is well known that the glycosylation of cell surface glycoproteins and glycolipids changes dramatically upon the malignant transformation of cells. We found that among six β-1,4-GalTs the gene expression of only β-1,4-GalT V increases upon malignant transformation. The expression of the β-1,4-GalT V gene has been shown to be regulated by transcription factors Sp1 and Ets-1 in cancer cells. Both transcription factors regulate the gene expression levels of not only glycosyltransferases, but also key molecules involved in tumor growth, invasion and metastasis. Therefore, the abnormal glycosylation and malignant phenotypes of cancer cells are considered to be suppressed by regulating the expression levels of the transcription factor genes. This review gives a summary account of the gene discovery, in vivo function, and transcriptional mechanism of β-1,4-GalT V. Also, a perspective on applications of the manipulation of transcription factor genes to cancer therapy will be discussed.