1996 Fiscal Year Final Research Report Summary
ANALYSIS OF ONCOGENS,TUMOR-SUPPRESSOR GENES,GROWTH FACTORS IN HUMAN HEPATOCELLULAR CARCINOMA AND THEIR APPLICATION TO TREATMENT
| Project/Area Number |
06670576
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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 | OSAKA CITY UNIVERSITY |
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Principal Investigator |
SEKI Shuichi OSAKA CITY UNIVERSITY,MEDICAL SCHOOL,LECTURER, 医学部, 講師 (50145778)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAGUCHI Hiroki OSAKA CITY UNIVERSITY,MEDICAL SCHOOL,ASSISTANT, 医学部, 助手 (40271184)
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| Project Period (FY) |
1994 – 1996
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| Keywords | Hepatocellular carcinoma / Apoptosis / Transforming growth factor-alpha / Epidermal growth factor receptor / Tyrosine kinase / Retinoblastoma gene product / DNA polymerase-alpha |
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| Research Abstract |
Some cell lines derived from four Japanese men with hepathocellular carcinomas (HCC) were established and designated OCUH-16, OCUH-A1, OCUH-Nuk1, and OCUH-Mas1. All of them have the morphological and chromosomal features of HCC.OCUH-16 and OCUH-A1 were used in this study. OCUH-16 cells were shown to express transforming growth factor-alpha (TGF-alpha) in addition to albumin. DNA polymerase-alpha, c-JUN,c-Fos, and retinoblastoma gene product (pRB) were also expressed in OCUH-16 cells. Electron microscopy revealed TGF-alpha immunoreactivity associated with the cell membrane, but TGF-alpha was not detected in medium conditioned by OCUH-16 cells by enzyme-linked immunosorbent assay. Reverse transcription and polymerase chain reaction analysis revealed the presence of TGF-alpha messenger RNA in the cells. Culture of OCUH-16 cells in the presence of a neutralizing antibody to TGF-alpha inhibited cell proliferation and induced many cells to undergo apoptosis. pRB was also actually detected immunohistochemically in human HCC tissues. The granules positive for pRB were found in the HCC cell nuclei and nuclei of sinusoidal cells (Kupffer cells, endothelial cells, lymphocytes, and stellate cells).pRB expression was well maintained in early and advanced HCC.The expression of pRB statistically correlated with that of DNA polymerase-alpha. The induction of apoptosis in HCC cells by inactivation of TGF-alpha may be applicable to clinical treatment.
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