Isolation of genes encoding NF-kB activator in adult T-cell leukemia
| Project/Area Number |
15590998
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Niigata University |
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Principal Investigator |
FUJII Masahiro Niigata University, Graduate School of Medical and Dental Sciences, Professor, 大学院・医歯学総合研究科, 教授 (30183099)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | HTLV-1 / NF-kB / ATL / Virus / Tax / Apoptosis / Leukemia / Oncogenesis / 発ガン / 感染 / トランスフォメーション |
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| Research Abstract |
Human T-cell leukemia virus type 1(HTLV-1) is associated with the development of adult T-cell leukemia(ATL). HTLV-1 encoded Taxi oncoprotein activates the transcription of genes involved in cell growth and anti-apoptosis through the NF-kB pathway, and is thought to play a critical role in the pathogenesis of ATL. While Tax1 expression is usually lost or minimal in ATL cells, these cells still show high constitutive NF-kB activity, indicating that genetic or epigenetic changes in ATL cells induce activation independent of Tax1. The aim of this study was to identify the molecules responsible for the constitutive activation of NF-kB in ATL cells using a retroviral functional cloning strategy. Using enhanced green fluorescent protein(EGFP) expression and blasticidin-resistance as selection markers, several retroviral cDNA clones exhibiting constitutive NF-kB activity in Rat-1 cells, including full-length CD30, were obtained from an ATL cell line. Exogenous stable expression of CD30 in Rat-1 cells constitutively activated NF-kB. Elevated expression of CD30 was identified in all ATL and HTLV-1 transformed T-cell lines examined, and primary ATL cells from a small number of patients. Elevated CD30 expression is considered one of the causes of constitutive NF-kB activation in ATL cells, and may be involved in ATL development.
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Report
(3 results)
Research Products
(23 results)
