The biosynthesis of the Sda histo-blood group antigen [Siaalpha2,3(GalNAcbeta1,4)Galbeta1,4GlcNAc-R], is catalyzed by Sda beta1,4GalNAc transferase (beta1,4GalNAc-T). This enzyme, which catalyzes the addition of GalNAc, the immunodominant sugar, to the Gal residue of an alpha2,3-sialylated type 2 chain, is highly expressed in normal colon but it is dramatically downregulated in colon cancer. The acceptor structure of beta1,4GalNAc-T is also a precursor of the biosynthesis of the sialyl Lewis x (sLex) antigen [Siaalpha2,3Galbeta1,4(Fuca1,3)GlcNAc-R], a major ligand for adhesion molecules of the selectin family whose ectopic expression in cancers favours metastasis formation. The fact that the precursor structures of the Sda and the sLex antigens are identical suggests a competition in the biosynthesis of the two structures and that the downregulation of beta1,4GalNAc-T opens the way to the biosynthesis of sLex, favouring the metastatic progression of colon cancer. The two beta1,4GalNAc-T mRNA species cloned to date differ in the first exon and predict two polypeptides with a different cytoplasmic tail: one encodes a polypeptide with an exceptionally long cytoplasmic sequence of 67 aminoacids, the other encodes a polypeptide with a cytoplasmic tail of 7 residues. To investigate the relationship between beta1,4GalNAc-T and sLex expression, we have stably expressed the two forms in the human colorectal cancer cell line LS174T, which expresses good level of sLex. Compared with mock-transfectants, the clones expressing either form of beta1,4GalNAc-T show a dramatic downregulation of sLex expression in FACS analysis, demonstrating that the level of expression of beta1,4GalNAc-T modulates the biosynthesis of sLex, in vitro.
The expression of Sda beta1,4 N-acetylgalactosaminyltransferase inhibits sialyl Lewis X expression in colon cancer cells
MALAGOLINI, NADIA;CHIRICOLO, MARIELLA;DALL'OLIO, FABIO
2005
Abstract
The biosynthesis of the Sda histo-blood group antigen [Siaalpha2,3(GalNAcbeta1,4)Galbeta1,4GlcNAc-R], is catalyzed by Sda beta1,4GalNAc transferase (beta1,4GalNAc-T). This enzyme, which catalyzes the addition of GalNAc, the immunodominant sugar, to the Gal residue of an alpha2,3-sialylated type 2 chain, is highly expressed in normal colon but it is dramatically downregulated in colon cancer. The acceptor structure of beta1,4GalNAc-T is also a precursor of the biosynthesis of the sialyl Lewis x (sLex) antigen [Siaalpha2,3Galbeta1,4(Fuca1,3)GlcNAc-R], a major ligand for adhesion molecules of the selectin family whose ectopic expression in cancers favours metastasis formation. The fact that the precursor structures of the Sda and the sLex antigens are identical suggests a competition in the biosynthesis of the two structures and that the downregulation of beta1,4GalNAc-T opens the way to the biosynthesis of sLex, favouring the metastatic progression of colon cancer. The two beta1,4GalNAc-T mRNA species cloned to date differ in the first exon and predict two polypeptides with a different cytoplasmic tail: one encodes a polypeptide with an exceptionally long cytoplasmic sequence of 67 aminoacids, the other encodes a polypeptide with a cytoplasmic tail of 7 residues. To investigate the relationship between beta1,4GalNAc-T and sLex expression, we have stably expressed the two forms in the human colorectal cancer cell line LS174T, which expresses good level of sLex. Compared with mock-transfectants, the clones expressing either form of beta1,4GalNAc-T show a dramatic downregulation of sLex expression in FACS analysis, demonstrating that the level of expression of beta1,4GalNAc-T modulates the biosynthesis of sLex, in vitro.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
