title: Enrichment of stem-like cell population comprises transformation ability of Epstein-Barr virus latent membrane protein 2A for non-transformed cells.
abstract: Epstein-Barr virus (EBV) is a representative human oncogenic virus that causes malignancies of various cell lineages. LMP2A, an EBV-encoded latent membrane protein, is expressed in EBV-associated malignancies of various cell lineages. LMP2A caused visible tumor formation transplanted in nude mice when transferred to immortalized non-transformed fibroblasts, NIH3T3. LMP2A-expressing cells showed higher ability of colony formation in soft agar than empty vector-transfected control cells, although the expression of LMP2A did not cause focus transformation in low serum concentrations. LMP2A expression increased the size of Hoechst 33,342 dye excreting side population (SP), in which cancer-initiating cells or cancer stem-like cells were enriched. SP increase by LMP2A was also responsible for colony formation in soft agar. The LMP2A-mediated SP increase depended on the activations of Stat3, MEK/ERK, and PI3K pathways, and on upregulation of HMGA2. Enrichment of SP, stem-like cells, by LMP2A promoted the transformation capability of LMP2A from non-transformed cells. The enrichment of stem-like cell population by a virus-encoded factor might explain the oncogenic functions of oncogenic viruses.
authors.affiliation: Department of Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Nakaya
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Kikuchi
authors.forename: Akiko
authors.initials: A
authors.lastname: Kunita
authors.forename: Shumpei
authors.initials: S
authors.lastname: Ishikawa
authors.forename: Keisuke
authors.initials: K
authors.lastname: Matsusaka
authors.forename: Rumi
authors.initials: R
authors.lastname: Hino
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
mesh_terms: D000818:Animals; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000472:pathogenicity*; D051379:Mice; D008819:Mice, Nude; D013234:Stem Cells / Q000821:virology*; D014763:Viral Matrix Proteins / Q000378:metabolism*
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins