| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Research Abstract |
Adult T-cell leukemia (ATL) is a T-cell neoplasm caused by Human T-cell leukemia virus type I infection. Previous reports described that the ubiquitin-editing enzyme A20 protects cytokine- or NK-induced cell death of endothelial cells via inhibiting caspase-8 activation. I found that the A20 protein and mRNA expressions were detectable in ATL cells in contrast to some of B-cell lymphoma cell lines with a somatic mutation and/or deletion of A20. Interestingly, quantitative RT-PCR analysis revealed that the A20 mRNA expression was frequently up-regulated in PBMCs derived from ATL patients. And A20 was found to be required for the growth of ATL-derived and HTLV-I-transformed cells. RNA-interference mediated knock-down of A20 induced the activation of apoptosis initiator caspase-8 concomitant with the activation of downstream effector caspase-3/7. In addition, I found that A20 physically interacts with caspase-8. Importantly, depletion of A20 suppressed the growth of ATL cells and increased the annexin V-positive population. These results suggest that A20 contributes to the survival of ATL cells and implicates A20 as a therapeutic molecular target for ATL therapy.
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