Role of CCAT/enhancer binding protein (C/EBP) α and C/EBP β in carcinogenesis. of hepatoblastoma and differentiation of hepatoblast.
| Project/Area Number |
14570726
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Chiba University |
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Principal Investigator |
TOMIZAWA Minoru Chiba University, University Hospital, Assistant, 医学部附属病院, 助手 (90334193)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAGAWARA Akira Chiba Cancer Center, Research Institute Division of Biochemistry, Head, 生化学研究部, 部長 (50117181)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| 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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| Keywords | hepatoblastoma / diagnosis / Cox hazard model / epatocyte differentiation / prognosis / transcription factor / C / EBP α / EBP β / 肝芽腫 / 肝癌 / 肝芽細胞 / 肝細胞分化 / 転写因子 / リアルタイム定量PCR / アデノウィルスベクター / 遺伝子治療 |
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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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Report
(3 results)
Research Products
(2 results)
