| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Research Abstract |
Background & Aims : Hepatoblastoma (HB) occurs from differentiation arrest of hepatocyte at hepatoblast. We analyzed the expression of CCAAT/enahncer binding protein (C/EBP)α and C/EBPβ that promote hepatocyte differentiation and inhibit proliferation of hepatocytes. Methods : Real-time quantitative PCR was performed to compare the expression of C/EBPα and C/EBPβ between tumor and non-tumor. Their expression was also analyzed Ath immunostaining. The expression levels of C/EBPα and C/EBPβ, were compared with clinoco-pathological data. Results : C/EBPα was up-regulated 2.23 times (P=0.013) and C/EBPβ was down-regulated 27% (P=0.002) in tumor as compared with non-tumor, as confirmed with immunostaining. C/EBPα was more up-regulated and C/EBPβ more down-regulated in poor differentiated part than well differentiated one in the same HB tumor immunohistochemically. Patients with higher expression of C/EBPα (P=0.05), and lower expression of C/EBPβ (P=0.025) than each median showed poor prognosis, respectively. With proportional Cox hazard model, hazard ratio of higher expression of C/EBPα, C/EBPβ, and poorly differentiated type were 3.57 (95% confidential interval, 0.91-14.0, P=0.068), 0.20 (0.04-0.96, P=0.044), and 13.5 (1.70-107, P=0.014), respectively. Conclusion : The analysis of expression of CIEBPα and C/EBPβ may be useful for precise diagnosis and prediction of prognosis of HB patients. CIEBPα may not act as a tumor suppressor in HB while C/EBPβ does. Since both C/EBPα and C/EBPβ promote hepatocyte differentiation, down-regulation of C/EBPβ led to the differentiation arrest and cell proliferation, and C/EBPα was up-regulated to compensate the role of C/EBPβ in hepatocyte differentiaion.
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