Regulation of the GnT-V promoter by transcription factor Ets-1 in various cancer cell lines.
Although the precise role of oligosaccharides in metastasis is presently unknown, numerous studies suggest that the beta1-6 branching structure of N-linked oligosaccharides plays a role in tumor metastasis. N-Acetylglucosaminyltransferase V (GnT-V), which catalyzes the formation of the beta1-6 branch, therefore appears to play a crucial role in tumor metastasis. Recently, we demonstrated that the expression of the GnT-V gene is regulated by a transcriptional factor, Ets-1 (Kang, R., Saito, H., Ihara, Y., Miyoshi, E., Koyama, N., Sheng, Y., and Taniguchi, N. (1996) J. Biol. Chem. 271, 26706-26712). In this study, we report an investigation of the general requirement for Ets-1 in the expression of GnT-V in cancer cell lines. In 16 cancer cell lines, the levels of GnT-V mRNA were closely correlated with ets-1 expression (r = 0.97; p < 0.0001). An increase in ets-1 levels by transfection of its cDNA led to an enhancement in GnT-V expression in cells that normally expressed low levels of ets-1. In contrast, the transfection of dominant negative ets-1 into cells that express high levels of ets-1 resulted in a decrease in GnT-V expression. Although Ets-1 cooperates with c-Jun in certain gene expressions, this was not the case in the regulation of the GnT-V gene. These results suggest that Ets-1 plays a significant role in regulating the expression of GnT-V in a variety of cancers and might be involved in the potential for malignancy via the action of GnT-V.
Ko
J H
JH
Department of Biochemistry, Osaka University Medical School, Room B1, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Miyoshi
E
E
Noda
K
K
Ekuni
A
A
Kang
R
R
Ikeda
Y
Y
Taniguchi
N
N
D001483:Base Sequence; D017931:DNA Primers; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics*; D011401:Promoter Regions, Genetic; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D018808:Transcription Factor AP-1 / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D017931:DNA Primers; C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D017351:N-Acetylglucosaminyltransferases; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase