Sensitization against Anticancer Drugs by Transfection with UBE2I Variant Gene into ras-NIH3H3 Mouse Fibroblasts

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 for 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. The UBE2I-v5-transfected cells were more sensitive than the parental cells to anticancer drugs such as vincristine (VCR), mitoxantrone (MIT) and etoposide (VP-16). 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 (replication protein A2), Rho-GDI (Rho guanine nucleotide dissociation inhibitor α), FUS (putative tumor suppressor) and TKT (transketolase) but negatively related to Per-1 (period-1), Ran (nuclear Ras-related protein), PTEN (phosphatase and tensin homolog), C/EBPα (CCAAT/enhancer binding protein α) and the tumor suppressor 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.