RRC ID 6526
著者 Senda M, Ito A, Tsuchida A, Hagiwara T, Kaneda T, Nakamura Y, Kasama K, Kiso M, Yoshikawa K, Katagiri Y, Ono Y, Ogiso M, Urano T, Furukawa K, Oshima S, Furukawa K.
タイトル 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.
ジャーナル Biochem J
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.
巻・号 402(3)
ページ 459-70
公開日 2007-3-15
DOI 10.1042/BJ20061118
PII BJ20061118
PMID 17123352
PMC PMC1863573
MeSH Cell Line DNA, Complementary / genetics Down-Regulation* Gangliosides / biosynthesis* Gene Expression Gene Expression Regulation, Neoplastic Glycosphingolipids / metabolism Humans Immunohistochemistry In Situ Hybridization Isoenzymes / classification Isoenzymes / genetics Isoenzymes / metabolism Kidney / enzymology* Kidney Neoplasms / enzymology* Kidney Neoplasms / genetics Kidney Neoplasms / pathology Kinetics Organ Specificity RNA, Messenger / genetics Sialyltransferases / classification Sialyltransferases / genetics Sialyltransferases / metabolism*
IF 4.097
引用数 27
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞