1992 Fiscal Year Final Research Report Summary
Mechanism and therapeutic application of the gangliosides specifically expressed in ATL and HTLV-I infected cells.
| Project/Area Number |
03671191
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | Nagasaki University School of Medicine |
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Principal Investigator |
FURUKAWA Koichi Nagasaki University School of Medicine, Department of Oncology Associate Professor, 医学部, 助教授 (80211530)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Yasuaki Nagasaki University School of Medicine, Atomic disease institute, Department of, 医学部, 助手 (60145232)
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| Project Period (FY) |
1991 – 1992
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| Keywords | ATL / HTLV-I / ganghioside / glycosyltransferase / GalNAc transferase / retrovirus / transactivation / expression cloning |
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| Research Abstract |
In order to investigate the regulatory mechanisms for the specific expression of GD2 ganglioside in ATL and HTLV-I infected cells, cDNA of beta1,4 GalNAc transferase(GM2/GD2 syn thase)gene was isolated by using eukaryotic cell expression cloning. This enzyme turned out to be type II membrane protein with 533 amino acids, anchoring on the Golgi membrane with transmembrane domain which is located near the N-terminus. Using this gene as a probe, following findings have been obtained.
1.High levels of expression of beta1,4 GalNAc transferase gene were demonstrated in ATL or HTLV-I positive cells by Northern blot and RT-PCR.
2.Expression of beta1,4 GalNAc transferse gene and HTLV-I p40^<tax> gene was examined by using leukemia cells from ATL patients with RT-PCR.In four out of 6 samples, definite expression of pX mRNA was detected. beta1,4 GalNac transferase mRNA was also detected in the same 4 samples.
3.Normal peripheral T lymphocytes expressing p40^<tax> with retroviral vector expressed high level of GD2, and also expressed high level of beta1,4 GalNac transferase gene in comparison with control sanples.
These results suggested that beta1,4 GalNAc transferase gene was being activated by transaction of p40^<tax>, resulting in the conversion of GD3 to GD2 in HTLV-I positive cells. In order to examine the molecular mechanisms for these regulations, beta1,4 GalNAc transferase gene was isolated and the exon-intron structne was analyzed. Activity and specificity of promoter/enhancer at 5' flanking region arenow being analyzed.
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Research Products
(6 results)
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[Publications] Furukawa,K.,Akagi,T.,Nagata,Y.,Yamade,Y.,Shiku,H.,Furukawa,K.: "GD2 ganglioside on human T-lymphotropic virus type I-in-fected T cells: possible activation of β1,4-N-acetylgalactosaminyltransferase gene by p40tax." Proc. Natl. Acad. Sci. USA.90. 1972-1976 (1993)
Description
「研究成果報告書概要(和文)」より
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[Publications] Yamashiro,S.,Tai,T.,Lloyd,K.O., Shiku,H.,Shutian,R.,Furukawa,K.Furukawa,K.: "Genetic and enzymatic basis for the differential expression of GM2 and GD2 gangliosides in human cancer cell lines." Cancer Res.53. 5395-5400 (1993)
Description
「研究成果報告書概要(和文)」より
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[Publications] Nagata, Y., Yamashiro, S., Yodoi, J., Shiku, H., Furukawa, K.et al.: "Expression cloning of beta1,4 N-acetylgalactosaminyltransferase cDNAs that determine the expression of GM2 and GD2 gangliosides." J.Biol.Chem.267. 12082-12089 (1992)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Furukawa, K., Akagi, T., Nagata, Y., Yamada, Y., Shiku, H., Furukawa, K.et al.: "GD2 ganglioside on human T-lymphotropic virus type I-infected T cells : Possible activation of beta1,4-N-acetylgalactosaminyltransferase gene by p40^<tax>." Proc.Natl.Acad.Sci.USA.1972-1976 (1993)
Description
「研究成果報告書概要(欧文)」より
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