| 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)
鹿股 直樹 神戸大学, 医学部, 助手 (60263373)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥7,900,000 (Direct Cost: ¥7,900,000)
Fiscal Year 1997: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥6,400,000 (Direct Cost: ¥6,400,000)
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| Keywords | HNF-1 / Hepatocellular carcinoma / Transcriptional regulation factor / RT-PCR / Differentiation / Nuclear protein / uPA / uPAR / 転写制御因子 / vHNF-1 / 組織分化 / 転写抑制因子 / 人体病理 / competitive RT-PCR |
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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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