title: UbcH10 is the cancer-related E2 ubiquitin-conjugating enzyme.
abstract: Ubiquitin-dependent proteolysis by the 26S proteasome plays a pivotal role in cell cycle progression as well as in tumorigenesis. In this pathway, ubiquitin-conjugating enzyme (E2), together with ubiquitin ligase (E3), transfers ubiquitin to the specific substrate protein(s); however, little is known about the potential contribution of E2 to tumorigenesis. In this study, we examined the expression levels of 17 E2 genes in 25 different human normal tissues and 24 human cancerous cell lines by using a quantitative real-time reverse transcription-PCR. Among the E2 gene family, the expression level of UbcH10 was extremely low in many of the normal tissues but prominent in the majority of cancerous cell lines. Intriguingly, UbcH10 was expressed at high levels in primary tumors derived from the lung, stomach, uterus, and bladder as compared with their corresponding normal tissues, suggesting that UbcH10 is involved in tumorigenesis or progression of the tumor. To further investigate a possible contribution of UbcH10 to malignant transformation and tumor cell proliferation, NIH3T3 cells were transfected with the expression plasmid encoding UbcH10, and stable transfectants were subsequently established. UbcH10-overexpressing cells exhibited an increased incorporation of bromodeoxyuridine, an enhanced growth rate, an increase in saturation density, and a promotion of colony formation in soft agar medium as compared with parental NIH3T3 cells and the control transfectants. Collectively, our present results provide the first evidence that UbcH10 is highly expressed in various human primary tumors and that UbcH10 has an ability to promote cell growth and malignant transformation.
authors.affiliation: Division of Biochemistry, Chiba Cancer Center Research Institute, Chiba 260-8717, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Toshinori
authors.initials: T
authors.lastname: Ozaki
authors.forename: Kou
authors.initials: K
authors.lastname: Miyazaki
authors.forename: Mineyoshi
authors.initials: M
authors.lastname: Aoyama
authors.forename: Masaru
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Akira
authors.initials: A
authors.lastname: Nakagawara
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002455:Cell Division / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D008025:Ligases / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured; D044763:Ubiquitin-Conjugating Enzymes
chemical_list: D012333:RNA, Messenger; C105156:UBE2C protein, human; D044763:Ubiquitin-Conjugating Enzymes; D008025:Ligases