Glycobiology Advance Access originally published online on July 27, 2006
Glycobiology 2006 16(11):1045-1051; doi:10.1093/glycob/cwl027
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Down-regulation of ß1,4-galactosyltransferase V is a critical part of etoposide-induced apoptotic process and could be mediated by decreasing Sp1 levels in human glioma cells
Key Laboratory of Medical Molecular Virology, Ministry of Education and Health, Gene Research Center, Shanghai Medical College of Fudan University (formerly Shanghai Medical University), Shanghai 200032, China
1 To whom correspondence should be addressed; e-mail: jxgu{at}shmu.edu.cn
Received on March 16, 2006; revised on July 21, 2006; accepted on July 23, 2006
ß1,4-Galactosyltransferase V (ß1,4GalT V; EC 2.4.1.38 [EC] ) is considered to be very important in glioma for expressing transformation-related highly branched N-glycans. Recently, we have characterized ß1,4GalT V as a positive growth regulator in several glioma cell lines. However, the role of ß1,4GalT V in glioma therapy has not been clearly reported. In this study, interfering with the expression of ß1,4GalT V by its antisense cDNA in SHG44 human glioma cells markedly promoted apoptosis induced by etoposide and the activation of caspases as well as processing of Bid and expression of Bax and Bak. Conversely, the ectopic expression of ß1,4GalT V attenuated the apoptotic effect of etoposide on SHG44 cells. In addition, both the ß1,4GalT V transcription and the binding of total or membrane glycoprotein with Ricinus communis agglutinin-I (RCA-I) were partially reduced in etoposide-treated SHG44 cells, correlated well with a decreased level of Sp1 that has been identified as an activator of ß1,4GalT V transcription. Collectively, our results suggest that the down-regulation of ß1,4GalT V expression plays an important role in etoposide-induced apoptosis and could be mediated by a decreasing level of Sp1 in SHG44 cells, indicating that inhibitors of ß1,4GalT V may enhance the therapeutic efficiency of etoposide for malignant glioma.
Key words: apoptosis / etoposide / glioma / Sp1 / ß1,4-galactosyltransferase V
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