Roles of oncogenes and growth factor receptors in hepatocarcinogenesis

Research Project

Project/Area Number	61570333
Research Category	Grant-in-Aid for General Scientific Research (C)
Allocation Type	Single-year Grants
Research Field	Gastroenterology
Research Institution	KANAZAWA UNIVERSITY
Principal Investigator	UNOURA Masashi (1987) The First Department of Internal Medicine, 医学部附属病院第一内科, 助手 (10175226) 田中延善 (1986) 金沢大, 医学部, 助手 (60163549)
Co-Investigator(Kenkyū-buntansha)	古沢明彦金沢大学, 医学部, 助手
Project Period (FY)	1986 – 1987
Project Status	Completed (Fiscal Year 1987)
Budget Amount *help	¥2,200,000 (Direct Cost: ¥2,200,000) Fiscal Year 1987: ¥800,000 (Direct Cost: ¥800,000) Fiscal Year 1986: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywords	oncogene / growth factor / 増殖因子 / 細胞増殖因子 / 膜レセプター
Research Abstract	Oncogenes and growth factor receptors were analyzed in hepatomas. Radioreceptor assays using <125D>I- labeled ligand revealed the high binding capacity of epidermal growth factor ( EGF ) and the low binding of insulin in PLC/ORF/5 and Hep G2 human hepatoma-derived cell lines. The binding of insulin-like growth factor-I ( IGF-I ) in PLC/PRF/5 cells was significantly higher than that in Hep G2 cells. Dot blot analyses of DNA and mRNA of the two cell lines showed expressions of all 12 oncogenes tested. There was no oncogene specifically expressed in hepatoma cells. EGF did enhanced the DNA synthesis of the hepatoma cells, but the oncogene expression did not change. We examined the oncogene products and growth factor-related proteins in surgically resected hepatoma tissues and the two hepatoma cell lines using an immunohistochemical method. EGF receptor was stained in the cell membrane of 4 out of 10 hepatoma tissues and the two hepatoma cell lines. The staining intensity was stronger in the cancerous portion than in the non-cancerous portion. The myc product was positive in the nuclei of 2 out of 10 hepatomas and in the two cell lines. The ras product was positive in the cytoplasm of the two cell lines, not in the hepatoma tissues. Neither EGF nor TGF was positive. From these, many oncogenes may be involved in the multistep hepatocarcinogenesis.