| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
NF-kB is an important transcription factor in cell proliferation. IkB inhibits transition of NF-kB into nucleus from cytoplasm. Mutation of IkB was reported in Hodgkin's lymphoma, resulting in over-expression of NF-kB and tumorigenesis. Similarly, over-expression of NF-kB was identified in adult T cell leukemia/lymphoma (ATLL). Therefore, in this study, we investigated alteration of IkB/NF-kB and its role in the effect of anti-tumor agent in ATLL.
To find expression and mutation of IkB, we performed RT-PCR following sequencing for whole exons of IkB in four ATLL cell lines (OKM2T, OKM3T, F6T, Su9T01) and primary ATLL cells derived from an acute ATLL patient as well as 10 non-ATLL cell lines. All samples expressed IkB. Mutation at codon 30 was identified in KS1/HHV8 associated lymphoma cell line, KS1. Additionally, silent mutation at codon 27 and 102 were seen in OKM2T and Su9T01, respectively.
Troglitazone and pioglitazone are one of thiazolidinediones that are high affinity ligand for the nuclear receptor called peroxisome proliferator-activated receptor gamma (PPAR-γ). Because Troglitazone is a moderately potent inhibitor of clonogenic growth of acute myeloid leukemia cells, we studied the effect of pioglitazone on ATLL. With 300 μM of pioglitazone, colony formation of ATLL cell lines (MT1, MT2, F6T, OKM3T, and Su9T01) was completely inhibited. Colony formation of HUT102, another ATLL cell line, was 12% compared to untreated control. Expression level of nuclear NF-kB in ATLL cells was not affected by pioglitazone treatment, suggesting that anti-tumor mechanisms of pioglitazone were not associated with IkB/NF-kB pathway, although pioglitazone had a strong anti-tumor effect on ATLL.
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