Expression of beta-galactoside alpha2,6 sialyltransferase and of alpha2,6-sialylated glycoconjugates in normal human liver, hepatocarcinoma, and cirrhosis.
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.
D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006023:Glycoproteins / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008103:Liver Cirrhosis / Q000201:enzymology*; D008113:Liver Neoplasms / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D012799:Sialyltransferases / Q000235:genetics*; D014158:Transcription, Genetic; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
D006023:Glycoproteins; D012333:RNA, Messenger; D012799:Sialyltransferases; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase