Overexpression of murine Pax3 increases NCAM polysialylation in a human medulloblastoma cell line.
Polysialic acid (PSA) is a developmentally regulated carbohydrate found primarily on neural cell adhesion molecules (NCAM) in embryonic tissues. The majority of NCAM in adult tissues lacks this unique carbohydrate, but polysialylated NCAM (PSA-NCAM) is present in adult brain regions where neural regeneration persists and in some pediatric brain tumors such as medulloblastoma, which show greater propensity for leptomeningeal spread. Pax3, a developmentally regulated paired homeodomain transcription factor, is thought to be involved in the regulation of neural cell adhesion molecules. Overexpression of murine Pax3 into a human medulloblastoma cell line (DAOY) resulted in an increase in NCAM polysialylation and a 2-4-fold increase in alpha2, 8-polysialyltransferase type II mRNA levels. No difference was observed in alpha2,8-polysialyltransferase type IV message. The addition of PSA to NCAM changed the adhesive behavior of these Pax3 transfectants. Transfectants expressing high PSA-NCAM show much less NCAM-dependent aggregation than those with less PSA-NCAM. In addition, Pax3 transfectants having high PSA-NCAM show heterophilic adhesion involving polysialic acid to heparan sulfate proteoglycan and agrin. These observations suggest that a developmentally regulated transcription factor, Pax3, could affect NCAM polysialylation and subsequently cell-cell and cell-substratum interaction.
Mayanil
C S
CS
Pediatric Brain Tumor Research Program, Department of Neurosurgery, Children's Memorial Institute of Education and Research, Chicago, Illinois 60614, USA.
George
D
D
Mania-Farnell
B
B
Bremer
C L
CL
McLone
D G
DG
Bremer
E G
EG
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006801:Humans; D008527:Medulloblastoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D012794:Sialic Acids / Q000378:metabolism*; D012799:Sialyltransferases / Q000378:metabolism; D014157:Transcription Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D004268:DNA-Binding Proteins; D019812:Heparan Sulfate Proteoglycans; D019006:Neural Cell Adhesion Molecules; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; D012794:Sialic Acids; D014157:Transcription Factors; C021319:polysialic acid; C068686:Pax3 protein, mouse; D012799:Sialyltransferases