title: B4GALNT2 gene expression controls the biosynthesis of Sda and sialyl Lewis X antigens in healthy and cancer human gastrointestinal tract.
abstract: The histo blood group carbohydrate Sd(a) antigen and its cognate biosynthetic enzyme B4GALNT2 show the highest level of expression in normal colon. Their dramatic down regulation previously observed in colon cancer tissues could play a role in the concomitant elevation of the selectin ligand sLe(x), involved in metastasis. However, down regulation of sLe(x) expression by B4GALNT2 has been so far demonstrated in vitro, but not in tissues. The human B4GALNT2 gene specifies at least two transcripts, diverging in the first exon, never studied in normal and cancer tissues. The long form contains a 253 nt exon 1L; the short form contains a 38 nt exon 1S. Using qPCR, we showed that cell lines and normal or cancerous colon, expressed almost exclusively the short form, while the long form was mainly expressed by the embryonic colon fibroblast cell line CCD112CoN. Immunochemistry approaches using colon cancer cells permanently expressing either B4GALNT2 cDNAs as controls, led to the observation of several protein isoforms in human normal and cancerous colon, and cell lines. We showed that tissues expressing B4GALNT2 protein isoforms were able to induce Sd(a) and to inhibit sLe(x) expression; both of which are expressed mainly on PNGase F-insensitive carbohydrate chains. Concomitant expression of B4GALNT2 and siRNA-mediated inhibition of FUT6, the major fucosyltransferase involved in sLe(x) synthesis in colon, resulted in a cumulative inhibition of sLe(x). In normal colon samples a significant relationship between sLe(x) expression and the ratio between FUT6/B4GALNT2 activities exists, demonstrating for the first time a role for B4GALNT2 in sLe(x) inhibition in vivo.
authors: Structural and Functional Glycobiology Unit, UMR CNRS 8576, University Lille Nord de France, Lille1, 59655 Villeneuve d'Ascq, France.
authors: Sophie
authors: S
authors: Groux-Degroote
authors: Structural and Functional Glycobiology Unit, UMR CNRS 8576, University Lille Nord de France, Lille1, 59655 Villeneuve d'Ascq, France.
authors: Cindy
authors: C
authors: Wavelet
authors: Structural and Functional Glycobiology Unit, UMR CNRS 8576, University Lille Nord de France, Lille1, 59655 Villeneuve d'Ascq, France.
authors: Marie-Ange
authors: MA
authors: Krzewinski-Recchi
authors: Structural and Functional Glycobiology Unit, UMR CNRS 8576, University Lille Nord de France, Lille1, 59655 Villeneuve d'Ascq, France.
authors: Lucie
authors: L
authors: Portier
authors: Structural and Functional Glycobiology Unit, UMR CNRS 8576, University Lille Nord de France, Lille1, 59655 Villeneuve d'Ascq, France.
authors: Marlène
authors: M
authors: Mortuaire
authors: Structural and Functional Glycobiology Unit, UMR CNRS 8576, University Lille Nord de France, Lille1, 59655 Villeneuve d'Ascq, France.
authors: Adriana
authors: A
authors: Mihalache
authors: Department of Medicine Clinical and Experimental (DMCS), University of Insubria Medical School, Varese, Italy.
authors: Marco
authors: M
authors: Trinchera
authors: Structural and Functional Glycobiology Unit, UMR CNRS 8576, University Lille Nord de France, Lille1, 59655 Villeneuve d'Ascq, France.
authors: Philippe
authors: P
authors: Delannoy
authors: Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.
authors: Nadia
authors: N
authors: Malagolini
authors: Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.
authors: Mariella
authors: M
authors: Chiricolo
authors: Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.
authors: Fabio
authors: F
authors: Dall'Olio
authors: Structural and Functional Glycobiology Unit, UMR CNRS 8576, University Lille Nord de France, Lille1, 59655 Villeneuve d'Ascq, France. Electronic address: anne.harduin@univ-lille1.fr.
authors: Anne
authors: A
authors: Harduin-Lepers
mesh_terms: D000328:Adult; D000368:Aged; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D005647:Fucosyltransferases / Q000096:biosynthesis* / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006031:Glycosylation; D006801:Humans; D016256:Lewis X Antigen / Q000096:biosynthesis* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017350:N-Acetylgalactosaminyltransferases / Q000096:biosynthesis*; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen
chemical_list: D018797:Cell Cycle Proteins; D016256:Lewis X Antigen; D009687:Nuclear Proteins; C490621:SDAD1 protein, human; D000080506:Sialyl Lewis X Antigen; D005647:Fucosyltransferases; D017350:N-Acetylgalactosaminyltransferases; C071413:beta-1,4-N-acetyl-galactosaminyl transferase 2; C515956:FUT6 protein, human
keywords: B4GALNT2; Colon cancer; Glycosylation; Glycosyltransferases; Sd(a) antigen