Yang Xuesong, Wang Jiao, Liu Shuiai, Yan Qiu
Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian, People's Republic of, China.
J Cell Biochem. 2014 Jan;115(1):168-78. doi: 10.1002/jcb.24645.
Lewis Y (LeY) is a carbohydrate tumor-associated antigen. The majority of cancer cells derived from epithelial tissues express LeY type difucosylated oligosaccharides. Fucosyltransferase IV (FUT4) is an essential enzyme that catalyzes the synthesis of LeY oligosaccharides. In a previous study we reported that FUT4 is associated with cell proliferation; however, despite the important role of FUT4 in cancer proliferation and apoptosis, little is known about the mechanisms underlying the regulation of FUT4 transcription. In the current study we investigated the regulation of FUT4 transcription in human breast cancer. We compared the regulation of human FUT4 gene transcription in human breast cancer cells (MCF-7 and MDA-MB-231) using promoter/luciferase analyses. Using a series of promoter deletion constructs, we identified a potential regulatory site located between 0.8 and 1.6 kb of the FUT4 promoter. As shown by EMSA and ChIP analyses, heat-shock factor 1 (HSF1) and Sp1are required for FUT4 promoter activity. In addition, we explored the role of HSF1 and Sp1 on cell proliferation, and found that the ERK1/2 MAPK and PI3K/Akt signaling pathways regulate the expression of FUT4, which play a role in cell proliferation via HSF1 and Sp1. These results suggest that FUT4 is a target gene for HSF1 and Sp1 that is required for cell cycle progression in breast cancer epithelial cells.
Lewis Y（LeY）是一种与肿瘤相关的碳水化合物抗原。大多数源自上皮组织的癌细胞表达LeY型二岩藻糖基化寡糖。岩藻糖基转移酶IV（FUT4）是催化LeY寡糖合成的关键酶。在之前的一项研究中，我们报道FUT4与细胞增殖有关；然而，尽管FUT4在癌症增殖和凋亡中起重要作用，但对FUT4转录调控的潜在机制知之甚少。在本研究中，我们调查了人乳腺癌中FUT4转录的调控情况。我们使用启动子/荧光素酶分析比较了人乳腺癌细胞（MCF-7和MDA-MB-231）中人类FUT4基因转录的调控。通过一系列启动子缺失构建体，我们在FUT4启动子的0.8至1.6 kb之间鉴定出一个潜在的调控位点。如电泳迁移率变动分析（EMSA）和染色质免疫沉淀（ChIP）分析所示，热休克因子1（HSF1）和Sp1是FUT4启动子活性所必需的。此外，我们探讨了HSF1和Sp1对细胞增殖的作用，发现ERK1/2丝裂原活化蛋白激酶（MAPK）和磷脂酰肌醇-3-激酶/蛋白激酶B（PI3K/Akt）信号通路调节FUT4的表达，FUT4通过HSF1和Sp1在细胞增殖中发挥作用。这些结果表明，FUT4是HSF1和Sp1的靶基因，是乳腺癌上皮细胞细胞周期进展所必需的。
