| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
1.hnRNP B1 is overexpressed in an early stage of lung cancers and premalignant lesions, such as bronchial dysplasia, suggesting that hnRNP B1 is involved in lung carcinogenesis. We recently found that hnRNP B1 interacted with DNA-dependent protein kinase (DNA-PK) complex, and the proteins were co-localized in the nucleus of lung cancer cell lines after irradiation. Furthermore, recombinant hnRNP B1 protein dose-dependently inhibited DNA-PK activity both in vitro and in intra cellular comet assay system. Using deletion mutants of hnRNP B1 and Ku proteins, regulatory subunits of DNA-PK, the responsible regions of hnRNP B1 for the interaction with DNA-PK complex were identified. In addition, recombinant hnRNP B1 protein inhibited the formation of holoenzyme of DNA-PK, dose dependently. Considering these results, we assume that the overexpression of hnRNP B1 occurring in the early stage of carcinogenesis inhibits DNA-PK activity, resulting in subsequent accumulation of erroneous rejoining of DNA double-strand breaks, causing tumor progression. To confirm the hypothesis, transgenic mice carrying a chimera gene of hnRNP B1 and surfactant protein C promoter, which overexpress hnRNP B1 in the lung, were established.
2.To determine the utility of plasma hnRNP B1 RNA and as cancer detection markers for lung cancer, we analyzed plasma hnRNP B1 mRNA of lung cancer patients by real-time RT-PCR. Plasma RNA was extracted from plasma of 44 lung cancer patients, 7 lung neoplasm patients, 24 benign lung diseases and 25 healthy volunteers. Mean concentration of plasma hnRNP B1 mRNA in lung cancer patients was 0.99 pg/μgRNA, whereas that in healthy volunteers and in benign lung diseases was 0.23 pg/μlRNA and 0.30pg/μlRNA, respectively (p<0.05). Twenty of 44 (45.5%) lung cancer patients showed more than 0.70pg/μlRNA of plasma hnRNP B1 mRNA, compared with only 3 of 25 (12.0%) healthy volunteers.
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