Human T-cell leukemia virus-1 encoded Tax protein transactivates alpha 1-->3 fucosyltransferase Fuc-T VII, which synthesizes sialyl Lewis X, a selectin ligand expressed on adult T-cell leukemia cells.
Leukemia cells in patients with adult T-cell leukemia (ATL) and related cell lines strongly express the carbohydrate determinant sialyl Lewis X, a ligand for selectins. Its expression is thought to be related closely to the extravascular infiltration of the leukemia cells. Human T-cell leukemia virus type 1 (HTLV-1), the etiological agent of ATL, produces Tax protein, which is implicated in leukemogenesis through its transactivating effect on various cellular genes. In this study we investigated the transactivating effect of HTLV-1 Tax on the alpha 1-->3 fucosyltransferase Fuc-T VII, the putative rate-limiting enzyme in the synthesis of sialyl Lewis X in human leukocytes using JPX-9 cells. JPX-9 is a subclone of a non-ATL human lymphocytic leukemia cell line, Jurkat, and was established by introducing a metallothionein promoter-driven Tax expression plasmid. The JPX-9 cells as well as parental Jurkat cells did not express Fuc-T VII mRNA under normal culture conditions. When cultured in the presence of 10 microM CdCl2, Tax was induced and a significant amount of the Fuc-T VII message was ascertained by Northern blotting. The amount of the message was 24.5 times as much as was detected in non-treated cells, and was comparable to that which appeared by TPA stimulation of the cells, which is supposed to simulate the sequence of events occurring in normal activation of T lymphocytes activated by more physiological stimuli. Sialyl Lewis X determinant was expressed at the surface of CdCl2-treated cells, while the determinant was not detectable on either unstimulated JPX-9 or parental Jurkat cells. These results indicate that expression of sialyl Lewis X on leukemic cells in patients with ATL is at least partly due to the transactivation of the Fuc-T VII gene induced by the HTLV-1 Tax, and suggest that this leads to the accelerated extravascular infiltration of ATL cells.
Hiraiwa
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Program of Experimental Pathology, Aichi Cancer Center, Nagoya, Japan.
Hiraiwa
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Kannagi
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R
D019256:Cadmium Chloride / Q000494:pharmacology; D005647:Fucosyltransferases / Q000235:genetics* / Q000378:metabolism; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D009844:Oligosaccharides / Q000096:biosynthesis*; D019087:Selectins / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D016356:Gene Products, tax; D008024:Ligands; D009844:Oligosaccharides; D019087:Selectins; D000080506:Sialyl Lewis X Antigen; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase; D019256:Cadmium Chloride; D013755:Tetradecanoylphorbol Acetate