Co-Investigator(Kenkyū-buntansha) |
TSUCHIMOCHI Makoto The Nippon Dental University, School of Dentistry at Niigata, Professor, 新潟歯学部, 教授 (20095186)
HARADA Mikiko The Nippon Dental University, School of Dentistry at Niigata, Lecturer, 新潟歯学部, 助手 (60339471)
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Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
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Research Abstract |
Rad9 is thought to be involved in the G2/M phase checkpoint and DNA repair. In this study, we have investigated the relationship between cell cycle and Rad9 expression in malignant cells. We examined Rad9 mRNA expression in normal human epidermal keratinocytes (NHEK(F)) and human oral squamous cell carcinoma cell line SCC-25 after UV irradiation. In both cells, Rad9 mRNA expression was increased 6 hour after UVB irradiation (0-3000mJ/cm2). Rad9 expression was also increased 2 hour after UVC irradiation (0-5500mJ/cm2) in SCC-25. Protein expression of Rad9 and cell-cycle control factors (p53, p21, p16, p38, ATR, Chk1, Cdc25B, CyclinB1, CyclinD1, and PCNA) was examined in NHEK(F), normal human gingival fibroblasts (HGF-1), human oral squamous cell carcinoma cell lines (SCC-9 and SCC-25), human skin malignant melanoma cell line (G-361), and immortalized human gingival keratinocytes (NDUSD-1). Rad9 expression in response to UVB (0-200J/m^2) or X-ray (2 Gy) irradiation, or hydroxyurea treatment (1mM or 10mM) was different among cells. The relationship between Rad9 and cell-cycle control factors was not clear. We have found that parathyroid hormone-related protein(PTHrP) expression was correlated with keratinization, differentiation, and histopathological grade of malignancy of oral squamous cell carcinoma. it has been suggested that PTHrP is involved in cell growth. Therefore, we expected that PTHrP was involved in cell-cycle regulation. But PTHrP expression after UVB(0-200J/m^2) or X-ray(2Gy) irradiation, or hydroxyurea treatment was different among cells and the relationship among PTHrP,Rad9 and cell-cycle control proteins was not clear. In this study, Rad9 mRNA expression was increased after high dose UV irradiation, but the relationship between cell cycle and Rad9 expressionin was not clear. Further study is needed to investigate the influence of Rad9 expression on tumor characteristics.
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