| Project/Area Number |
14570466
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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 |
Gastroenterology
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
NISHIDA Naoshi Kyoto University, Graduate School of Medicine, instructor, 医学研究科, 助手 (60281755)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUDA Yoshihiro Kyoto University, Faculty of Medicine, professor, 医学部, 教授 (50127130)
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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 |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Hepatocellular carcinoma / P53 pathway / p14 gene / chromosomal instability / deletion / methylation / carcinogenesis / 突然変異 / 発癌 |
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| Research Abstract |
We investigated mutation, deletion and aberrant methylation of the p14^<ARF> gene in 44 human hepatocellular carcinoma by using PCR-SSCP, direct sequencing, multiplex-PCR and methylation specific-PCR. In addition, we studied expression of p14^<ARF> with Real-Time PCR, expression of p53 with immunohistochemistry and examined chromosomalinstability by using semiquantitative microsatellite analysis. We found mutation of p14^<ARF> in two HCCs and deletion in one HCC, however aberrant promoter methylation was not detected in any cases.
Examination of Real-Time PCR revealed that overexpression of p14^<ARF> was detected in all but one HCC with p14^<ARF> deletion, suggesting that aberration of transcriptional regulation was not take place during hepatocarcinogenesis. In addition, p14^<ARF> overexpression was associated with poorly differentiated phenotype. All three HCCs with p14^<ARF> alteration were well-differentiated. On the other hand, twelve HCCs showed aberration of p53 with immunohistochemistry and only one was well-differentiated HCC among them. These data indicate that p53 pathway play an important role in a subset of HCC formation.
Chromosomal alteration was observed in all HCCs examined including well-differentiated HCC and p53 pathway aberration may accelerate chromosomal instability of HCC cell expanding altered chromosomal region and contribute to it's progression.
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