| Budget Amount *help |
¥3,950,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
It is important to investigate the interferon-alpha (IFN-a) sensitivity-related gene and regulation of susceptibility to IFN-α in renal cell carcinoma (RCC). First, we have identified seven candidate genes, which are associated with IFN-a-response and then established prediction formula using four genes, I.e. ADFP, MITF, MTUS1, and TNNT1, in RCC cell lines. Validation of this prediction model was performed in other RCC cell lines, including primary culture cells from patients with RCC. We next focused MITF gene, which individually correlated with IFN-α-sensitivity, to analyze relationship between its expression and IFN-α-response status by gene transfection. MITF transfectant demonstrated susceptibility in IFN-α-resistant line as compared with wild type or mock transfectant. Because MITF is one off transcription factor, which can bind to p16 and HIF-1α, it is suggested that MITF may be associated with development and progression of RCC acceleration of cell cycle. Thus, we evaluated expression of p16 and anti-tumor effect of biological active p16 peptide (p16-MIS) by peptide transduction system with Wr-T transporter peptide. All RCC cell lines used are absent for p16 protein, even in the IFN-α-resistant RCC MITF-transfectant. P16-MIS successfully transferred into cellular cytoplasm and nucleus of RCC cells by concentration dependent manner. Interestingly, IFN-α-susceptibility was acquired at 2.5 to 100 times intensity in IFN-α-resistant RCC cell line. These results suggested that IFN-α-response related gene, MITF and its related cell cycle regulator, p16 could be molecular targets in therapeutic strategy of RCC.
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