Regulation of metastasis-suppressive gene Nm23-H1 on glycosyl-transferases involved in the synthesis of sialyl Lewis antigens.
By using reverse transcriptase-polymerase chain reaction (RT-PCR), the mRNA expressions of three families of glycosyltransferases involved in the synthesis of sialyl Lewis antigens were determined in H7721 human hepatocarcinoma cell line before and after the transfection of metastasis-suppressive gene nm23-H1. These glycosyltransferases included alpha1,3fucosyltransferase (alpha1,3FucT)-III, -IV, -VI, -VII, and -IX, alpha2,3-sialyltransferase (ST3Gal)-I, -II, -III, and -IV as well as O-glycan core 2 beta1,6 N-acetylglucosaminyltransferase (C2GnT)-I and -II. In mock cells transfected with the vector, the expression-order of alpha1,3FucTs was IV>VI>III>VII>IX, that of ST3Gals was IV>I>II>III, and that of C2GnT was I>II. Nm23-H1 downregulated the mRNA expressions of all five subtypes of alpha1,3FucT and -I, -III, -IV subtypes of ST3Gal, but not ST3Gal-II and C2GnT-I, II. On the other hand, the expressions of cell surface sialyl Lewis X (SLe(x)) and alpha2,3 sialyl residues were decreased on nm23-H1 transfected cells as detected with monoclonal antibody of SLe(x) and enzyme-labeled lectins, respectively. Since SLe(x) was reported to be a metastasis-associated glycan structure, the reduced expressions of SLe(x) and some enzymes related to its synthesis may be one of the mechanisms to explain the metastasis-suppressive effect of nm23-H1.
Duan
Ling-Ling
LL
Key Laboratory of Glycoconjugate Research, Ministry of Health, Department of Biochemistry, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Guo
Peng
P
Zhang
Ying
Y
Chen
Hui-Li
HL
D000941:Antigens / Q000096:biosynthesis*; D001483:Base Sequence; D017931:DNA Primers; D005434:Flow Cytometry; D016695:Glycosyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000276:immunology*; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000941:Antigens; D017931:DNA Primers; D007983:Lewis Blood Group Antigens; D054778:NM23 Nucleoside Diphosphate Kinases; D012333:RNA, Messenger; D016695:Glycosyltransferases; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase