title: 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 E21 (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 (VP16). The regression analysis of the total chemosensitivity pattern of UBE2I-vS-transfected cells revealed that the function of UBE2I-v5 was positively related to RPA2 (replication protein A2), Rho-GDI (Rho guanine nucleotide dissociation inhibitor a), FUS (putative tumor suppressor) and TKT (transketolase) but negatively related to Per-1 (period-I), Ran (nuclear Ras-related protein), PTEN (phosphatase and tensin homolog), C/EBPalpha (CCAAT/enhancer binding protein a) and the tumor suppressor p53. Thus, it is possible that UBE21-v5 plays a role in carcinogenesis by suppressing the function of CIEBPa and/or p53 via RPA2-like activity.
authors.affiliation: Departments of Frontier Surgery, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba, Japan.
authors.forename: Tooru
authors.initials: T
authors.lastname: Shiratori
authors.forename: Hideaki
authors.initials: H
authors.lastname: Shimada
authors.forename: Akiko
authors.initials: A
authors.lastname: Kagaya
authors.forename: Mari
authors.initials: M
authors.lastname: Kuboshima
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nabeya
authors.forename: Toshio
authors.initials: T
authors.lastname: Machida
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Goto
authors.forename: Masaki
authors.initials: M
authors.lastname: Takiguchi
authors.forename: Takenori
authors.initials: T
authors.lastname: Ochiai
authors.forename: Takaki
authors.initials: T
authors.lastname: Hiwasa
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000201:enzymology / Q000235:genetics; D018076:DNA, Complementary / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D004938:Esophageal Neoplasms / Q000097:blood / Q000201:enzymology / Q000235:genetics; D005047:Etoposide / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology* / Q000502:physiology; D011905:Genes, ras; D051379:Mice; D008942:Mitoxantrone / Q000494:pharmacology; D041681:NIH 3T3 Cells; D014162:Transfection; D044763:Ubiquitin-Conjugating Enzymes / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014750:Vincristine / Q000494:pharmacology; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D000970:Antineoplastic Agents; D018076:DNA, Complementary; D014750:Vincristine; D005047:Etoposide; D008942:Mitoxantrone; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9