Transcriptional regulation of the human Sia-alpha2,3-Gal-beta1,4-GlcNAc-R:alpha2,8-sialyltransferase (hST8Sia III) by retinoic acid in human glioblastoma tumor cell line.

Abstract

In this study, we have shown the transcriptional regulation of the human Sia-alpha2,3-Gal-beta1,4-GlcNAc-R:alpha2,8-sialyltransferase (hST8Sia III) induced by retinoic acid (RA), a potent neuronal cell regulator in glioblastoma cell line (U-87MG). The induction of hST8Sia III by RA is regulated at the transcriptional level in a dose- and time-dependent manner, as evidenced by reverse transcription-polymerase chain reaction (RT-PCR). To elucidate the mechanism underlying the regulation of hST8Sia III gene expression in RA-stimulated U-87MG cells, we characterized the promoter region of the hST8Sia III gene. Functional analysis of the 5'-flanking region of the hST8Sia III gene by the transient expression method showed that the -1194 to -816 region, which contains a retinoic acid nucleic receptor (RAR) at -1000 to -982, functions as the RA-inducible promoter in U-87MG cells. Site-directed mutagenesis indicated that the RA binding site at -996 to -991 is crucial for the RA-induced expression of the hST8Sia III in U-87MG cells. In addition, the transcriptional activity of hST8Sia III induced by RA in U-87MG cells was strongly inhibited by SP600125, c-Jun N-terminal Kinase (JNK) inhibitor, as determined by RT-PCR and luciferase assay of hST8Sia III promoter containing the -1194 to -816 regions. These results suggest that RA markedly modulates transcriptional regulation of hST8Sia III gene expression through JNK signal pathway in U-87MG cells.

• Authors: Seok-Jo Kim, Hee-Jung Choi, Un-Ho Jin, Young-Choon Lee, Cheorl-Ho Kim
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1759 Issue 10 Pg. 451-7 (Oct 2006) ISSN: 0006-3002 [Print] Netherlands
• PMID: 17069899 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Tretinoin
• DNA
• Sia(alpha2,3)Gal(beta1,4)GlcNAc alpha-2,8-sialyltransferase
• Sialyltransferases

Topics

• Base Sequence
• Brain Neoplasms (enzymology, genetics, pathology)
• Cell Line, Tumor
• DNA
• Gene Expression Regulation, Enzymologic (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Glioblastoma (enzymology, genetics, pathology)
• Humans
• Molecular Sequence Data
• Reverse Transcriptase Polymerase Chain Reaction
• Sialyltransferases (genetics)
• Transcriptional Activation (drug effects)
• Tretinoin (pharmacology)