Inokuchi Jin-ichi, Kabayama Kazuya, Uemura Satoshi, Igarashi Yasuyuki
Department of Biomembrane and Biofunctional Chemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo, Nishi 6-chome, Kita-ku, Sapporo 060-0812, Japan.
Glycoconj J. 2004;20(3):169-78. doi: 10.1023/B:GLYC.0000024248.62242.1f.
To elucidate the biological significance of the lactosylceramide (LacCer) branching in glycosphingolipid (GSL) biosynthesis, we established ganglioside GM3- and lactosylsulfatide SM3-reconstituted cells by introducing the GM3 synthase gene and the sulfotransferase gene, respectively. In SM3-expressing cells, the reduction of beta1 integrin mRNA expression, the reduced adhesivity to fibronectin and laminin, and the suppression of anchorage-independent growth (tumorigenic potential) were observed. On the other hand, in GM3-expressing cells, anchorage-independent growth was promoted and the expression of PDGF alpha receptor mRNA was specifically reduced. Interestingly enough, no change in anchorage-dependent growth was observed in these cells, and tumorigenic signals were controlled selectively in both positive and negative directions. Thus, the spatio-temporal, gene expression control mechanism by individual GSL molecules accumulating in the cell membrane microdomain (raft) has been proven.
为阐明糖鞘脂（GSL）生物合成中乳糖基神经酰胺（LacCer）分支的生物学意义，我们分别通过导入GM3合酶基因和磺基转移酶基因，建立了神经节苷脂GM3和乳糖基硫酸鞘脂SM3重构细胞。在表达SM3的细胞中，观察到β1整合素mRNA表达降低、对纤连蛋白和层粘连蛋白的粘附性降低以及锚定非依赖性生长（致瘤潜力）受到抑制。另一方面，在表达GM3的细胞中，锚定非依赖性生长得到促进，且血小板衍生生长因子α受体mRNA的表达特异性降低。有趣的是，在这些细胞中未观察到锚定依赖性生长的变化，并且致瘤信号在正负两个方向上均被选择性地控制。因此，已证明细胞膜微区（脂筏）中积累的单个GSL分子的时空基因表达控制机制。
