Relationship between Elevated FX Expression and Increased Production of GDP-l-Fucose, a Common Donor Substrate for Fucosylation in Human Hepatocellular Carcinoma and Hepatoma Cell Lines

作者: Koichi Honke , Eiji Miyoshi , Michela Tonetti , Akinori Kasahara , Susumu Nakahara

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摘要: The levels of fucosylated glycoproteins in various cancers and inflammatory processes have been a subject intense study. level fucosyltransferases intracellular GDP-L-fucose, sugar nucleotide common donor substrate for all fucosyltransferases, may regulate the glycoproteins. This study reports on determination GDP-L-fucose human hepatocellular carcinoma (HCC) surrounding tissues, using recently established high-throughput assay system. Levels HCC tissues were significantly increased compared with adjacent nontumor or normal livers. mean +/- SD was 3.6 0.2 micro mol/mg control liver, 4.6 0.9 noninvolved liver (chronic hepatitis, 4.4 0.7 mol/mg; cirrhosis, 4.8 mol/mg), 7.1 2.5 tissues. decreased proportion tumor size (r = -0.675, P 0.0002). When expression series genes responsible synthesis investigated, gene FX found to be 70% (7 10) examined that their positively correlated mRNA 0.599, 0.0074). some hepatoma hepatocyte cell lines determined. production strongly HepG2 Chang moderately Hep3B HLF, and, HLE, similar tissue. To investigate effect core fucosylation, cDNA transfected into cells, which express relatively low GDP-L-fucose:N-acetyl-beta-D-glucosaminide alpha1-6 fucosyltransferase (alpha1-6 FucT) mRNA. Transfection this caused an increase as well extent fucosylation glycoproteins, including alpha-fetoprotein, judged by reactivity lectins. Collectively, results herein suggest high is dependent followed increases enhancement FucT expression. Thus, elevation up-regulation represent potential markers HCC.

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