title: Identification and expression of a sialyltransferase responsible for the synthesis of disialylgalactosylgloboside in normal and malignant kidney cells: downregulation of ST6GalNAc VI in renal cancers.
abstract: Although disialyl glycosphingolipids such as GD3 and GD2 have been considered to be associated with malignant tumours, whether branched-type disialyl glycosphingolipids show such an association is not well understood. We investigated the sialyltransferases responsible for the biosynthesis of DSGG (disialylgalactosylgloboside) from MSGG (monosialylgalactosylgloboside). Among six GalNAc:alpha2,6-sialyltransferases cloned to date, we focused on ST6GalNAc III, V and VI, which utilize sialylglycolipids as substrates. In vitro enzyme analyses revealed that ST6GalNAc III and VI generated DSGG from MSGG with V(max)/K(m) values of 1.91 and 4.16 respectively. Transfection of the cDNA expression vectors for these enzymes resulted in DSGG expression in a renal cancer cell line. Although both ST6GalNAc III and VI genes were expressed in normal kidney cells, the expression profiles of ST6GalNAc VI among 20 renal cancer cell lines correlated clearly with those of DSGG, suggesting that the sialyltransferase involved in the synthesis of DSGG in the kidney is ST6GalNAc-VI. ST6GalNAc-VI and DSGG were found in proximal tubule epithelial cells in normal kidney tissues, while they were downregulated in renal cancer cell lines and cancer tissues. All these findings indicated that DSGG was suppressed during the malignant transformation of the proximal tubules as a maturation arrest of glycosylation.
authors.affiliation: Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Senda
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ito
authors.forename: Akiko
authors.initials: A
authors.lastname: Tsuchida
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hagiwara
authors.forename: Tsuguhiro
authors.initials: T
authors.lastname: Kaneda
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Kenji
authors.initials: K
authors.lastname: Kasama
authors.forename: Makoto
authors.initials: M
authors.lastname: Kiso
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: Yoko
authors.initials: Y
authors.lastname: Katagiri
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Ono
authors.forename: Manabu
authors.initials: M
authors.lastname: Ogiso
authors.forename: Takeshi
authors.initials: T
authors.lastname: Urano
authors.forename: Keiko
authors.initials: K
authors.lastname: Furukawa
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oshima
authors.forename: Koichi
authors.initials: K
authors.lastname: Furukawa
mesh_terms: D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D015536:Down-Regulation; D005732:Gangliosides / Q000096:biosynthesis*; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006028:Glycosphingolipids / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000145:classification / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000201:enzymology*; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D007700:Kinetics; D009928:Organ Specificity; D012333:RNA, Messenger / Q000235:genetics; D012799:Sialyltransferases / Q000145:classification / Q000235:genetics / Q000378:metabolism*
chemical_list: D018076:DNA, Complementary; D005732:Gangliosides; D006028:Glycosphingolipids; D007527:Isoenzymes; D012333:RNA, Messenger; C086047:disialosyl galactosyl globoside; C476449:GalNAc sialyltransferase VI; D012799:Sialyltransferases