1997 Fiscal Year Final Research Report Summary
Analysis of how liver-specific transcriptional regulation factors are implicated in hepatocytic differentiation and oncogenesis ; their application for histo- and clinicopathological diagnosis
| Project/Area Number |
07457050
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | KOBE UNIVERSITY |
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Principal Investigator |
HAYASHI Yoshitake Kobe University Pathology I,Associate Professor, 医学部, 助教授 (50189669)
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| Co-Investigator(Kenkyū-buntansha) |
SAIJOH Kiyofumi Kanazawa University Hygiene, Professor, 医学部, 教授 (00178469)
ITOH Hiroshi Kobe University Pathology I,Professor, 医学部, 教授 (40168373)
SANO Kimihiko Kobe University Hospital Pediatrics, Lecturer, 医学部, 講師 (40205993)
HANIOKA Keisuke Kobe University Hospital Pathology, Associate Professor, 医学部・附属病院, 助教授 (70127463)
MATOZAKI Takashi Kobe University Hospital Internal Medicine II,Research Associate, 医学部・附属病院, 助手 (80252782)
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| Project Period (FY) |
1995 – 1997
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| Keywords | HNF-1 / Hepatocellular carcinoma / Transcriptional regulation factor / RT-PCR / Differentiation / Nuclear protein / uPA / uPAR |
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| Research Abstract |
Hepatic nuclear factor 1 (HNF-1), as a transcription regulator, binds the promoters or enhancers of genes expressed almost exclusively in liver. We have previously reported that the ratio of HNF-1alpha and HNF-1beta mRNA is related to histological differentiation of hepatocellular carcinoma (HCC) (Ninomiya T et al., J Hepatol, 25 : 445-453,1996). Furthermore, to investigate the expression pattern in HCCs, we relatively quantitatively compared the expression of HNF-1alpha and HNF-1beta proteins in various histologically differentiated cancerous as well as surrounding noncancerous tissues and their binding activity for B element in alpha-fetoprotein enhaner. The polyclonal antibodies for human HNF-1alpha and HNF-1beta were generated by Glutathione S-transferase fussion protein. Nuclear extracts were prepared from the tested tissues. The expression of HNF-1alpha and HNF-1beta proteins in isolated nuclei were measured by western blotting and their binding activity examined by gel mobility assay. Immunohistochemistry were performed in frozen and parafin embedded sections. Western blottings demonstrated that HNF-1alpha protein was overexpressed in well differentiated HCC tissues but decreased from well differentiated to poorly differentiated HCCs compared with surrounding non-HCC tissues. The HNF-1beta expression did not after from well differentiated to poorly differentiated HCCs athough it is more abundant in cancerous tissues than the surrounding noncancerous portions. In gel mobility assay, the decreasing tendency was shown in the assay of HNF-1alpha binding activity. These findings provide an evidence involved in effect of HNF-1alpha alteration on the differentiations of HCC that the histological differentiation of HCC turns poor when HNF-1alpha expression decreases and HNF-1beta competes to bind the elements formerly occupied by HNF-1alpha (Wang W et al., J Pathol in press).
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[Publications] Morita Y,Hayashi Y,Suzuki S,Kawasaki K,Ohta K,Kanamaru T,Yamamoto M,Saito Y,Ito H,Wang Y,Doe WF.: "Expression of Urokinase-type Plasminogen Activator Receptor in Hepatocellular Carcinoma." Hepatol. 25. 856-861 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kim SR,Hayashi Y,Hamada K,Shintani S,Sasaki K,Park SY,Ryang MK,Taniguchi M,Kim KI,Kim MM,Itoh H,Saeki K,Nukata I,Yoon S.: "Prediction of efficancy of interferon treatment of chronic hepatitis C by new classification of chronic hepatitis." Pathol International. (in press).
Description
「研究成果報告書概要(欧文)」より
