title: Identification of BC005512 as a DNA damage responsive murine endogenous retrovirus of GLN family involved in cell growth regulation.
abstract: Genotoxicity assessment is of great significance in drug safety evaluation, and microarray is a useful tool widely used to identify genotoxic stress responsive genes. In the present work, by using oligonucleotide microarray in an in vivo model, we identified an unknown gene BC005512 (abbreviated as BC, official full name: cDNA sequence BC005512), whose expression in mouse liver was specifically induced by seven well-known genotoxins (GTXs), but not by non-genotoxins (NGTXs). Bioinformatics revealed that BC was a member of the GLN family of murine endogenous retrovirus (ERV). However, the relationship to genotoxicity and the cellular function of GLN are largely unknown. Using NIH/3T3 cells as an in vitro model system and quantitative real-time PCR, BC expression was specifically induced by another seven GTXs, covering diverse genotoxicity mechanisms. Additionally, dose-response and linear regression analysis showed that expression level of BC in NIH/3T3 cells strongly correlated with DNA damage, measured using the alkaline comet assay,. While in p53 deficient L5178Y cells, GTXs could not induce BC expression. Further functional studies using RNA interference revealed that down-regulation of BC expression induced G1/S phase arrest, inhibited cell proliferation and thus suppressed cell growth in NIH/3T3 cells. Together, our results provide the first evidence that BC005512, a member from GLN family of murine ERV, was responsive to DNA damage and involved in cell growth regulation. These findings could be of great value in genotoxicity predictions and contribute to a deeper understanding of GLN biological functions.
authors.affiliation: Center for Drug Safety Evaluation and Research, State Key Laboratory of New Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yuanfeng
authors.initials: Y
authors.lastname: Wu
authors.forename: Xinming
authors.initials: X
authors.lastname: Qi
authors.forename: Likun
authors.initials: L
authors.lastname: Gong
authors.forename: Guozhen
authors.initials: G
authors.lastname: Xing
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.forename: Lingling
authors.initials: L
authors.lastname: Miao
authors.forename: Jun
authors.initials: J
authors.lastname: Yao
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Chie
authors.initials: C
authors.lastname: Furihata
authors.forename: Yang
authors.initials: Y
authors.lastname: Luan
authors.forename: Jin
authors.initials: J
authors.lastname: Ren
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D020077:Endogenous Retroviruses / Q000235:genetics*; D051379:Mice; D009153:Mutagens / Q000494:pharmacology*; D041681:NIH 3T3 Cells; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D009153:Mutagens; D011506:Proteins