A NOVEL IMMUNE-REGULATORY GENE EJ3AG9: ITS CORRELATION WITH IIEPATOCELLULAR CARCINOMA AND ACUTE REJECTION AFTER LIVER TRANSPLANTATION.

Research Project

Project/Area Number	14571181
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Digestive surgery
Research Institution	The University of Tokyo
Principal Investigator	MIKI Kenji The Univ. of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (10242059)
Co-Investigator(Kenkyū-buntansha)	INOUE Satoshi The Univ. of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (40251251) IMAMURA Hiroshi The Univ. of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (00283268)
Project Period (FY)	2002 – 2003
Project Status	Completed (Fiscal Year 2003)
Budget Amount *help	¥3,500,000 (Direct Cost: ¥3,500,000) Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000) Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywords	EBAG9 / HEPATOCELLULAR CARCINOMA / DEDIFFERENTIATION / TUMOR PROLIFERATION / MULTISTEP TUMOR PROGRESSION / IMMUNOHISTOCHEMISTRY / 移植免疫 / 急性拒絶反応 / 細胞増殖
Research Abstract	The estrogen-responsive gene EBAG9, whose product is identical to cancer cell surface antigen RCAS1, is reported to be associated with tumor progression and invasiveness in various carcinomas. In this study we examined the expression of EBAG9/RCAS 1 in hepatocellular carcinoma (HCC), with special reference to its relationship with the stepwise evolution of HCC. Expression was examined by immunohistochemistry and Western blot analysis in 143 HCCs, as well as in non-cancerous liver tissue. Then the association between enhanced EBAG9/RCAS1 expression and various clinicopathological parameters including Ki-67 labeling index (LI), a marker of proliferative activity, was evaluated. There was a constant low level of EBAG9/RCAS 1 expression in non-cancerous liver tissue, with a regular cytoplasmic distribution. Positive immunoreactivity for EBAG9/RCAS1 was detected on the surface and in the cytoplasm of 84 HCC tumors, with an irregular staining pattern. Enhanced EBAG9/ROASi expression was correlated with a lower degree of differentiation and Kt67 LI. Interestingly, expression was enhanced specifically in the less differentiated lesions within "nodule-in-nodule" tumours. In conclusion, EBAG9/RCAS1 was associated with HCC tumour dedifferentiation and increased proliferative activity.