Biol. Pharm. Bull. 29(12) 2372—2377 (2006)

flammatory cytokine primarily produced by activated macrophages in response to inflammation, lipopolysaccharide and other bacterial products and has been implicated in the pathogenesis of various diseases such as rheumatoid arthritis and inflammatory bowel disease. TNFa interacts with TNF receptor-1 (TNFR-1) in most tissues and TNFR-2 in the lymphoid system and activates multiple signal transduction pathways, such as nuclear factor kB (NFkB) and Jun N-terminal kinase; it also activates the death-inducing signaling complex to induce immune and inflammatory responses and apoptosis. NFkB is bound to the inhibitory protein IkB in the cytoplasm of uninduced cells. After stimulation with TNFa and interleukin-1 (IL-1), IkB is phosphorylated, ubiquitylated and degraded. Subsequently, NFkB is released and translocated to the nucleus to activate the expression of various target genes. Eight members of the NFkB/Rel family have been cloned and characterized; the most abundant form is a heterodimer of the p50 and p65 subunits, the latter comprising a powerful transcriptional activation domain. Biosynthesis of O-glycans is initiated by GalNAc addition to Ser and Thr and is followed by sequential addition of monosaccharides by specific glycosyltransferases. O-glycans on mucins are divided into three structural regions: core, backbone and peripheral regions. Based on their sequence similarities and linkage types, nine human FUT genes have been cloned and classified into three groups: a1,2-FUTs (FUT I and II), a1,3-FUTs (FUT III, IV, V, VI VII and IX) and a1,6-FUT (FUT VIII). Fifteen or more human ST cDNAs have also been cloned and characterized based on their substrate specificities: ST3Gal I to V, ST6Gal I, ST3GalNAc I to VI, and ST8Sia I to V. Each of the ST genes is differentially expressed in a tissue-, cell type-, and stagespecific manner. It has previously been reported that expression of FUT IV mRNA is moderately and ST3Gal I mRNA prominently increased in human colorectal cancer tissues and that FUT III, FUT VI and ST3Gal IV are the most abundantly expressed and FUT IV, ST3Gal II, ST3Gal I and ST6Gal I are increased in colorectal carcinoma. These reports have indicated that FUT III and IV and ST3Gal I and IV are mainly responsible for the biosynthesis of distal glycans such as Lewis-type antigens. However, ST3Gal I, elevated in primary breast carcinomas, is responsible for adding sialic acid to core 1 and thereby terminating chain extension. In this report, we determined the mRNA expression levels of FUTs and STs after stimulation with TNFa in the human colon adenocarcinoma cell line HT-29 and NFkB-p65 knockdown HT-29 cells, and clarified that ST3Gal I mRNA expression is transcriptionally up-regulated by TNFa stimulation through NFkB binding sites.