Dall'Olio Fabio, Chiricolo Mariella, D'Errico Antonia, Gruppioni Elisa, Altimari Annalisa, Fiorentino Michelangelo, Grigioni Walter F
Department of Experimental Pathology, F. Addarii Institute of Oncology, University of Bologna, Via S. Giacomo 14, 40126 Bologna, Italy.
Glycobiology. 2004 Jan;14(1):39-49. doi: 10.1093/glycob/cwh002. Epub 2003 Sep 26.
beta-Galactoside alpha2,6-sialyltransferase (ST6Gal.I) mediates the addition of alpha2,6-linked sialic acid to glycoproteins. ST6Gal.I is strongly expressed by the liver and is up-regulated in several cancers, but little is known of its regulation in human liver diseases. We have investigated the expression of ST6Gal.I and its product, the alpha2,6-sialylated lactosamine, in normal human liver, hepatocarcinoma (HCC), and cirrhosis. We found that both ST6Gal.I activity and mRNA can undergo up- or down-regulation in different HCC patients. At the mRNA level, the groups of specimens showing the highest expression were HCC of grade 2, HCC developed without preexisting cirrhosis, and HCC of male patients. The lectin from Sambucus nigra (SNA) reveals a significative overexpression of alpha2,6-sialylated glycoconjugates in HCC tissue homogenates and their intracellular accumulation in HCC histological sections, even though in a few cases the extent of alpha2,6-sialylation dramatically decreases. Transcription of the gene occurs through at least two different promoters, resulting in two differentially expressed mRNA species. RNA in situ hybridization reveals that the ST6Gal.I mRNA can be expressed at a quantitatively heterogeneous level among the neoplastic cells. Neither ST6Gal.I expression nor alpha2,6-sialylation are altered in cirrhosis. These data indicate that neoplastic transformation but not cirrhosis can alter the process of alpha2,6-sialylation of liver glycoproteins.
β-半乳糖苷α2,6-唾液酸转移酶（ST6Gal.I）介导α2,6-连接的唾液酸添加到糖蛋白上。ST6Gal.I在肝脏中强烈表达，并且在几种癌症中上调，但对其在人类肝脏疾病中的调控了解甚少。我们研究了ST6Gal.I及其产物α2,6-唾液酸化乳糖胺在正常人类肝脏、肝癌（HCC）和肝硬化中的表达。我们发现，在不同的HCC患者中，ST6Gal.I活性和mRNA均可发生上调或下调。在mRNA水平上，表达最高的标本组为2级HCC、无预先存在肝硬化的HCC以及男性患者的HCC。黑接骨木（SNA）凝集素显示，HCC组织匀浆中α2,6-唾液酸化糖缀合物有显著过表达，并且在HCC组织切片中有细胞内积聚，尽管在少数情况下α2,6-唾液酸化程度显著降低。该基因的转录通过至少两个不同的启动子进行，产生两种差异表达的mRNA。RNA原位杂交显示，ST6Gal.I mRNA在肿瘤细胞中的表达水平在数量上是异质的。肝硬化中ST6Gal.I表达和α2,6-唾液酸化均未改变。这些数据表明，肿瘤转化而非肝硬化可改变肝脏糖蛋白的α2,6-唾液酸化过程。
