Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study, we have shown that KCl known as an inducer for differentiation of neuronal cells increases the human Sia-alpha2,3-Gal-beta1,4-GlcNAc-R:alpha2,8-sialyltransferase (hST8Sia III) gene transcription via phosphoinositide 3 kinase (PI-3K) in glioblastoma U-87MG cells. The induction of hST8Sia III by KCl 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 U-87MG cells induced by KCl, 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 functions as the KCl-inducible promoter in U-87MG cells. Furthermore, as evidenced by Western blot analysis and RT-PCR, KCl-induced expression of hST8Sia III gene was dependent on the PI-3K signal transduction pathway during the neuronal differentiation of U-87 cells, as an increase in beta-tubulin III known as a neuronal differentiation marker was observed. In KCl-depolarization on U-87 cells, the PI-3K-dependent promoter activation at the -1194 to -816 region up-regulated expression of hST8Sia III gene. These results suggest that the expression of hST8Sia III gene via the PI-3K signaling pathway is enhanced during KCl-induced differentiation of U-87 cells by increasing expression of beta-tubulin III.
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PMID:Molecular mechanisms involved in transcriptional activation of the human Sia-alpha2,3-Gal-beta1,4-GlcNAc-R:alpha2,8-sialyltransferase (hST8Sia III) gene induced by KCl in human glioblastoma cells. 1664 48

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.
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PMID: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. 1706 99