Expression of gangliosides, GD1a, and sialyl paragloboside is regulated by NF-κB-dependent transcriptional control of α2,3-sialyltransferase I, II, and VI in human castration-resistant prostate cancer cells
Expression of gangliosides, GD1a, and sialyl paragloboside is regulated by NF-κB-dependent transcriptional control of α2,3-sialyltransferase I, II, and VI in human castration-resistant prostate cancer cells
复制标题
DOI：
10.1002/ijc.25860
复制
发表时间：
2011-10-15
影响因子：
6.4
通讯作者：
Kaneda, Yasufumi
中科院分区：
文献类型：
--
作者：
Hatano, Koji;Miyamoto, Yasuhide;Kaneda, Yasufumi
神经节苷脂是一种含有唾液酸的鞘糖脂，与肿瘤的恶性程度和进展有关。在产生神经节苷脂所需的酶中，唾液酸转移酶因其与癌症的关系而受到广泛关注。在我们以前的报告中，神经节苷脂GD 1a和唾液酸paragloboside（SPG），一种新的乳糖系列神经节苷脂，更丰富的PC 3和DU 145细胞，去势抵抗性前列腺癌细胞，与前列腺癌敏感细胞和正常前列腺上皮细胞相比。GD 1a由GM 1通过α 2，3唾液酸转移酶（ST 3Gal）I合成，主要由ST 3Gal II合成。合成SPG的酶是ST 3Gal VI。去势抵抗性前列腺癌细胞中GD 1a和SPG的高产量分别与ST 3Gal II和VI的高表达相关。佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）可轻度诱导ST 3 Gal I和II的表达，NF-κ B诱饵寡核苷酸（ODN）可抑制PMA诱导的ST 3 Gal I和ST 3 Gal II的表达，而AP-1诱饵ODN则不能抑制PMA诱导的ST 3 Gal I和ST 3 Gal II的表达。在NF-κ B家族的五种哺乳动物同源物中，RelB RNAi最有效地抑制ST 3Gal I和ST 3Gal II的表达。RelB RNAi也最有效地抑制了ST 3Gal VI的表达。在PC 3细胞中，RelB siRNA处理显著降低GD 1a和SPG的量。因此，去势抵抗性前列腺癌细胞中GD 1a和SPG的产生是由NF-κ B间接控制的，主要是由RelB通过ST 3Gal I、II和VI的转录调节。
Gangliosides are sialic acid-containing glycosphingolipids that are associated with tumor malignancy and progression. Among the enzymes required for the production of gangliosides, sialyltransferases have received much attention in terms of their relationship with cancer. In our previous report, ganglioside GD1a and sialyl paragloboside (SPG), a neolacto-series ganglioside, were much more abundant in PC3 and DU145 cells, castration-resistant prostate cancer cells, as compared with hormone-sensitive prostate cancer cells and normal prostate epithelium. GD1a is synthesized from GM1 by alpha 2,3 sialyltransferase (ST3Gal) I and mainly by ST3Gal II. The enzyme to synthesize SPG is ST3Gal VI. The high production of GD1a and SPG in castration-resistant prostate cancer cells was correlated with the high expression of ST3Gal II and VI, respectively. The expression of ST3Gal I and II was mildly induced by phorbol-12-myristate-13-acetate (PMA), and PMA-induced expression of ST3Gal I and ST3Gal II was inhibited by NF-kappa B decoy oligodeoxynucleotides (ODN) but not by AP-1 decoy ODN. Among the five mammalian homologs of the NF-kappa B family, RelB RNAi most effectively inhibited the expression of ST3Gal I and ST3Gal II. The expression of ST3Gal VI was also most effectively inhibited by RelB RNAi. The amount of GD1a and SPG was significantly reduced by RelB siRNA treatment in PC3 cells. Thus, the production of GD1a and SPG in castration-resistant prostate cancer cells was indirectly controlled by NF-kappa B, mainly by RelB, through the transcriptional regulation of ST3Gal I, II, and VI.