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Proc Natl Acad Sci U S A. Jun 6, 1995; 92(12): 5724–5728.

Elevated expression of H type GDP-L-fucose:beta-D-galactoside alpha-2-L-fucosyltransferase is associated with human colon adenocarcinoma progression.


GDP-L-fucose:beta-D-galactoside alpha-2-L-fucosyltransferase (EC is a key enzyme in the biosynthesis of fucosylated type 1 and 2 lactoseries structures, such as Lewis b and the H type 2 and Lewis Y, respectively, that are accumulated in colon adenocarcinoma. Analysis of the mRNA transcript level for the human H gene-encoded beta-D-galactoside alpha-2-L-fucosyltransferase revealed 40- and 340-fold increases in the mRNA levels in all adenocarcinomas and tumor cell lines, respectively, compared to normal colon mucosa where a low level of mRNA transcript was detected. A variable increase in mRNA transcript levels was observed in 50% of adenomatous polyps. Nucleotide sequence analysis of the protein coding region of the cDNAs derived from normal colon, adenoma, and colon adenocarcinoma revealed 100% homology, suggesting that there are no tumor-associated allelic variations within the H beta-D-galactoside alpha-2-L-fucosyltransferase cDNA. These results suggest that beta-D-galactoside alpha-2-L-fucosyltransferase expression highly correlates with malignant progression of colon adenocarcinoma.

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  • Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990 Jun 1;61(5):759–767. [PubMed]
  • Hakomori S. Aberrant glycosylation in tumors and tumor-associated carbohydrate antigens. Adv Cancer Res. 1989;52:257–331. [PubMed]
  • Magnani JL, Brockhaus M, Smith DF, Ginsburg V, Blaszczyk M, Mitchell KF, Steplewski Z, Koprowski H. A monosialoganglioside is a monoclonal antibody-defined antigen of colon carcinoma. Science. 1981 Apr 3;212(4490):55–56. [PubMed]
  • Brown A, Ellis IO, Embleton MJ, Baldwin RW, Turner DR, Hardcastle JD. Immunohistochemical localization of Y hapten and the structurally related H type-2 blood-group antigen on large-bowel tumours and normal adult tissues. Int J Cancer. 1984 Jun 15;33(6):727–736. [PubMed]
  • Blaszczyk M, Pak KY, Herlyn M, Sears HF, Steplewski Z. Characterization of Lewis antigens in normal colon and gastrointestinal adenocarcinomas. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3552–3556. [PMC free article] [PubMed]
  • Ernst C, Atkinson B, Wysocka M, Blaszczyk M, Herlyn M, Sears H, Steplewski Z, Koprowski H. Monoclonal antibody localization of Lewis antigens in fixed tissue. Lab Invest. 1984 Apr;50(4):394–400. [PubMed]
  • Blaszczyk-Thurin M, Thurin J, Hindsgaul O, Karlsson KA, Steplewski Z, Koprowski H. Y and blood group B type 2 glycolipid antigens accumulate in a human gastric carcinoma cell line as detected by monoclonal antibody. Isolation and characterization by mass spectrometry and NMR spectroscopy. J Biol Chem. 1987 Jan 5;262(1):372–379. [PubMed]
  • Sakamoto J, Furukawa K, Cordon-Cardo C, Yin BW, Rettig WJ, Oettgen HF, Old LJ, Lloyd KO. Expression of Lewisa, Lewisb, X, and Y blood group antigens in human colonic tumors and normal tissue and in human tumor-derived cell lines. Cancer Res. 1986 Mar;46(3):1553–1561. [PubMed]
  • Cordon-Cardo C, Lloyd KO, Sakamoto J, McGroarty ME, Old LJ, Melamed MR. Immunohistologic expression of blood-group antigens in normal human gastrointestinal tract and colonic carcinoma. Int J Cancer. 1986 May 15;37(5):667–676. [PubMed]
  • Abe K, Hakomori S, Ohshiba S. Differential expression of difucosyl type 2 chain (LeY) defined by monoclonal antibody AH6 in different locations of colonic epithelia, various histological types of colonic polyps, and adenocarcinomas. Cancer Res. 1986 May;46(5):2639–2644. [PubMed]
  • Ruggiero F, Cooper HS, Steplewski Z. Immunohistochemical study of colorectal adenomas with monoclonal antibodies against blood group antigens (sialosyl-Le(a), Le(a), Le(b), Le(x), Le(y), A, B, and H). Lab Invest. 1988 Jul;59(1):96–103. [PubMed]
  • Kim YS, Yuan M, Itzkowitz SH, Sun QB, Kaizu T, Palekar A, Trump BF, Hakomori S. Expression of LeY and extended LeY blood group-related antigens in human malignant, premalignant, and nonmalignant colonic tissues. Cancer Res. 1986 Nov;46(11):5985–5992. [PubMed]
  • Le Pendu J, Cartron JP, Lemieux RU, Oriol R. The presence of at least two different H-blood-group-related beta-D-gal alpha-2-L-fucosyltransferases in human serum and the genetics of blood group H substances. Am J Hum Genet. 1985 Jul;37(4):749–760. [PMC free article] [PubMed]
  • Beyer TA, Hill RL. Enzymatic properties of the beta-galactoside alpha 1 leads to 2 fucosyltransferase from porcine submaxillary gland. J Biol Chem. 1980 Jun 10;255(11):5373–5379. [PubMed]
  • Kumazaki T, Yoshida A. Biochemical evidence that secretor gene, Se, is a structural gene encoding a specific fucosyltransferase. Proc Natl Acad Sci U S A. 1984 Jul;81(13):4193–4197. [PMC free article] [PubMed]
  • Sarnesto A, Köhlin T, Thurin J, Blaszczyk-Thurin M. Purification of H gene-encoded beta-galactoside alpha 1----2 fucosyltransferase from human serum. J Biol Chem. 1990 Sep 5;265(25):15067–15075. [PubMed]
  • Sarnesto A, Köhlin T, Hindsgaul O, Thurin J, Blaszczyk-Thurin M. Purification of the secretor-type beta-galactoside alpha 1----2-fucosyltransferase from human serum. J Biol Chem. 1992 Feb 5;267(4):2737–2744. [PubMed]
  • Orntoft TF, Greenwell P, Clausen H, Watkins WM. Regulation of the oncodevelopmental expression of type 1 chain ABH and Lewis(b) blood group antigens in human colon by alpha-2-L-fucosylation. Gut. 1991 Mar;32(3):287–293. [PMC free article] [PubMed]
  • Blaszczyk-Thurin M, Sarnesto A, Thurin J, Hindsgaul O, Koprowski H. Biosynthetic pathways for the Leb and Y glycolipids in the gastric carcinoma cell line KATO III as analyzed by a novel assay. Biochem Biophys Res Commun. 1988 Feb 29;151(1):100–108. [PubMed]
  • Yazawa S, Nakamura J, Asao T, Nagamachi Y, Sagi M, Matta KL, Tachikawa T, Akamatsu M. Aberrant alpha 1-->2fucosyltransferases found in human colorectal carcinoma involved in the accumulation of Leb and Y antigens in colorectal tumors. Jpn J Cancer Res. 1993 Sep;84(9):989–995. [PubMed]
  • Limas C. Detection of urothelial Lewis antigens with monoclonal antibodies. Am J Pathol. 1986 Dec;125(3):515–523. [PMC free article] [PubMed]
  • Langkilde NC, Wolf H, Orntoft TF. Lewis antigen expression in benign and malignant tissues from RBC Le(a-b-) cancer patients. Br J Haematol. 1991 Nov;79(3):493–499. [PubMed]
  • Phillips ML, Nudelman E, Gaeta FC, Perez M, Singhal AK, Hakomori S, Paulson JC. ELAM-1 mediates cell adhesion by recognition of a carbohydrate ligand, sialyl-Lex. Science. 1990 Nov 23;250(4984):1130–1132. [PubMed]
  • Berg EL, Robinson MK, Mansson O, Butcher EC, Magnani JL. A carbohydrate domain common to both sialyl Le(a) and sialyl Le(X) is recognized by the endothelial cell leukocyte adhesion molecule ELAM-1. J Biol Chem. 1991 Aug 15;266(23):14869–14872. [PubMed]
  • Garrigues J, Anderson J, Hellström KE, Hellström I. Anti-tumor antibody BR96 blocks cell migration and binds to a lysosomal membrane glycoprotein on cell surface microspikes and ruffled membranes. J Cell Biol. 1994 Apr;125(1):129–142. [PMC free article] [PubMed]
  • Larkin M, Ahern TJ, Stoll MS, Shaffer M, Sako D, O'Brien J, Yuen CT, Lawson AM, Childs RA, Barone KM, et al. Spectrum of sialylated and nonsialylated fuco-oligosaccharides bound by the endothelial-leukocyte adhesion molecule E-selectin. Dependence of the carbohydrate binding activity on E-selectin density. J Biol Chem. 1992 Jul 5;267(19):13661–13668. [PubMed]
  • Miyake M, Hakomori SI. A specific cell surface glycoconjugate controlling cell motility: evidence by functional monoclonal antibodies that inhibit cell motility and tumor cell metastasis. Biochemistry. 1991 Apr 2;30(13):3328–3334. [PubMed]
  • Leibovitz A, Stinson JC, McCombs WB, 3rd, McCoy CE, Mazur KC, Mabry ND. Classification of human colorectal adenocarcinoma cell lines. Cancer Res. 1976 Dec;36(12):4562–4569. [PubMed]
  • Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. [PubMed]
  • Larsen RD, Ernst LK, Nair RP, Lowe JB. Molecular cloning, sequence, and expression of a human GDP-L-fucose:beta-D-galactoside 2-alpha-L-fucosyltransferase cDNA that can form the H blood group antigen. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6674–6678. [PMC free article] [PubMed]
  • Nakajima-Iijima S, Hamada H, Reddy P, Kakunaga T. Molecular structure of the human cytoplasmic beta-actin gene: interspecies homology of sequences in the introns. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6133–6137. [PMC free article] [PubMed]
  • Seed B, Aruffo A. Molecular cloning of the CD2 antigen, the T-cell erythrocyte receptor, by a rapid immunoselection procedure. Proc Natl Acad Sci U S A. 1987 May;84(10):3365–3369. [PMC free article] [PubMed]
  • Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. [PMC free article] [PubMed]
  • Hansson GC, Karlsson KA, Larson G, McKibbin JM, Blaszczyk M, Herlyn M, Steplewski Z, Koprowski H. Mouse monoclonal antibodies against human cancer cell lines with specificities for blood group and related antigens. Characterization by antibody binding to glycosphingolipids in a chromatogram binding assay. J Biol Chem. 1983 Apr 10;258(7):4091–4097. [PubMed]
  • Thurin J, Thurin M, Kimoto Y, Herlyn M, Lubeck MD, Elder DE, Smereczynska M, Karlsson KA, Clark WM, Jr, Steplewski Z, et al. Monoclonal antibody-defined correlations in melanoma between levels of GD2 and GD3 antigens and antibody-mediated cytotoxicity. Cancer Res. 1987 Mar 1;47(5):1229–1233. [PubMed]
  • Young WW, Jr, Portoukalian J, Hakomori S. Two monoclonal anticarbohydrate antibodies directed to glycosphingolipids with a lacto-N-glycosyl type II chain. J Biol Chem. 1981 Nov 10;256(21):10967–10972. [PubMed]
  • Blaszczyk M, Hansson GC, Karlsson KA, Larson G, Stromberg N, Thurin J, Herlyn M, Steplewski Z, Koprowski H. Lewis blood group antigens defined by monoclonal anti-colon carcinoma antibodies. Arch Biochem Biophys. 1984 Aug 15;233(1):161–168. [PubMed]
  • Cooper HS, Malecha MJ, Bass C, Fagel PL, Steplewski Z. Expression of blood group antigens H-2, Le(y), and sialylated-Le(a) in human colorectal carcinoma. An immunohistochemical study using double-labeling techniques. Am J Pathol. 1991 Jan;138(1):103–110. [PMC free article] [PubMed]
  • Yago K, Zenita K, Ginya H, Sawada M, Ohmori K, Okuma M, Kannagi R, Lowe JB. Expression of alpha-(1,3)-fucosyltransferases which synthesize sialyl Le(x) and sialyl Le(a), the carbohydrate ligands for E- and P-selectins,in human malignant cell lines. Cancer Res. 1993 Nov 15;53(22):5559–5565. [PubMed]
  • Mollicone R, Gibaud A, François A, Ratcliffe M, Oriol R. Acceptor specificity and tissue distribution of three human alpha-3-fucosyltransferases. Eur J Biochem. 1990 Jul 20;191(1):169–176. [PubMed]
  • Sarnesto A, Köhlin T, Hindsgaul O, Vogele K, Blaszczyk-Thurin M, Thurin J. Purification of the beta-N-acetylglucosaminide alpha 1----3-fucosyltransferase from human serum. J Biol Chem. 1992 Feb 5;267(4):2745–2752. [PubMed]
  • Weston BW, Smith PL, Kelly RJ, Lowe JB. Molecular cloning of a fourth member of a human alpha (1,3)fucosyltransferase gene family. Multiple homologous sequences that determine expression of the Lewis x, sialyl Lewis x, and difucosyl sialyl Lewis x epitopes. J Biol Chem. 1992 Dec 5;267(34):24575–24584. [PubMed]
  • Trail PA, Willner D, Lasch SJ, Henderson AJ, Hofstead S, Casazza AM, Firestone RA, Hellström I, Hellström KE. Cure of xenografted human carcinomas by BR96-doxorubicin immunoconjugates. Science. 1993 Jul 9;261(5118):212–215. [PubMed]
  • Sawada R, Lowe JB, Fukuda M. E-selectin-dependent adhesion efficiency of colonic carcinoma cells is increased by genetic manipulation of their cell surface lysosomal membrane glycoprotein-1 expression levels. J Biol Chem. 1993 Jun 15;268(17):12675–12681. [PubMed]

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