Functional analysis of UBE2I varinat gene isolated by SEREX screening using the sera of patients with esophageal squamous cell carcinoma

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 17591320
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Chiba University
• Principal Investigator: SHIRATORI Toru CHIBAUNIVERSITY, HOSPITAL, RESEARCH ASSISTANT, 医学部附属病院, 助手 (80361434)
• Co-Investigator(Kenkyū-buntansha): SHIMADA Hideaki Chiba University, GRADUATE SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 大学院医学研究院, 講師 (20292691) ; HIWASA Takaki Chiba University, GRADUATE SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 大学院医学研究院, 助教授 (30260251) ; OCHIAI Takenori Chiba University, GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 大学院医学研究院, 教授 (80114255)
• Project Period (FY): 2005 – 2006
• Keywords: Esophageal cancer / squamous cell carcinoma / UBE2I / SEREX

Research Abstract

We previously performed SEREX (serological identification of antigens by recombinant expression cloning) using the sera of patients with esophageal squamous cell carcinoma (SCC), and isolated a variant clone (AK093616) of ubiquitin-conjugating enzyme E2I (UBE2I). This clone was tentatively designated as UBE2I-v5 and analyzed the biological function by transient transfection of the cDNA into activated Ha-ras-transformed NIH3T3 (ras-NIH) mouse fibroblasts. Chemosensitivity to 92 cytotoxic drugs was compared between UBE2I-v5-transfected cells and the parental ras-NIH cells. UBE2I-v5-transfected cells were more sensitive to anticancer drugs such as vincristine, mitoxantrone and etoposide than the parental cells. The regression analysis of the total chemosensitivity pattern of UBE2I-v5-transfected cells revealed that the function of UBE2I-v5 was positively related to RPA2, Rho-GDI, FUS and TKT but negatively related with Per-I, Ran, PTEN, C/EBPα and p53. Thus, it is possible that UBE2I-v5 plays a role in carcinogenesis by suppressing the function of C/EBPα and/or p53 via RPA2-like activity.