title: In vivo and in vitro studies suggest a possible involvement of HPV infection in the early stage of breast carcinogenesis via APOBEC3B induction.
abstract: High prevalence of infection with high-risk human papilloma virus (HPV) ranging from 25 to 100% (average 31%) was observed in breast cancer (BC) patients in Singapore using novel DNA chip technology. Early stage of BC demonstrated higher HPV positivity, and BC positive for estrogen receptor (ER) showed significantly higher HPV infection rate. This unique association of HPV with BC in vivo prompted us to investigate a possible involvement of HPV in early stages of breast carcinogenesis. Using normal breast epithelial cells stably transfected with HPV-18, we showed apparent upregulation of mRNA for the cytidine deaminase, APOBEC3B (A3B) which is reported to be a source of mutations in BC. HPV-induced A3B overexpression caused significant γH2AX focus formation, and DNA breaks which were cancelled by shRNA to HPV18 E6, E7 and A3B. These results strongly suggest an active involvement of HPV in the early stage of BC carcinogenesis via A3B induction.
authors.affiliation: Infectious Disease program, Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ohba
authors.affiliation: Infectious Disease program, Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Koji
authors.initials: K
authors.lastname: Ichiyama
authors.affiliation: Infectious Disease program, Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Misako
authors.initials: M
authors.lastname: Yajima
authors.affiliation: TOSHIBA Research & Development Center, TOSHIBA Corporation, Kawasaki, Kanagawa, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Gemma
authors.affiliation: Materials and Devices Division, TOSHIBA Corporation, Minato-ku, Tokyo, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Nikaido
authors.affiliation: Infectious Disease program, Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Infectious Disease program, Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor Darul Ehsan, Malaysia.
authors.forename: PeiPei
authors.initials: P
authors.lastname: Chong
authors.affiliation: Pathogen Genomics Center, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Mori
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Rain
authors.initials: R
authors.lastname: Yamamoto
authors.affiliation: Department of Hematology-Medical Oncology, National University Cancer Institute, the Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: John Eu Li
authors.initials: JE
authors.lastname: Wong
authors.affiliation: Infectious Disease program, Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D063646:Carcinogenesis; D002472:Cell Transformation, Viral; D003564:Cytidine Deaminase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D042822:Genomic Instability; D057809:HEK293 Cells; D006801:Humans; D042361:Mammary Glands, Human / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D027383:Papillomaviridae / Q000502:physiology*; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism; D013997:Time Factors
chemical_list: D015778:Minor Histocompatibility Antigens; D011960:Receptors, Estrogen; C495794:APOBEC3B protein, human; D003564:Cytidine Deaminase