title: Regulation of human genome expression and RNA splicing by human papillomavirus 16 E2 protein.
abstract: Human papillomavirus 16 (HPV16) is causative in human cancer. The E2 protein regulates transcription from and replication of the viral genome; the role of E2 in regulating the host genome has been less well studied. We have expressed HPV16 E2 (E2) stably in U2OS cells; these cells tolerate E2 expression well and gene expression analysis identified 74 genes showing differential expression specific to E2. Analysis of published gene expression data sets during cervical cancer progression identified 20 of the genes as being altered in a similar direction as the E2 specific genes. In addition, E2 altered the splicing of many genes implicated in cancer and cell motility. The E2 expressing cells showed no alteration in cell growth but were altered in cell motility, consistent with the E2 induced altered splicing predicted to affect this cellular function. The results present a model system for investigating E2 regulation of the host genome.
authors.affiliation: VCU Philips Institute for Oral Health Research, Virginia Commonwealth University School of Dentistry, Department of Oral and Craniofacial Molecular Biology, Richmond, VA 23298, USA; University of Glasgow Institute of Infection, Immunology and Inflammation, Glasgow G12 8QQ, UK.
authors.forename: Elaine J
authors.initials: EJ
authors.lastname: Gauson
authors.affiliation: VCU Philips Institute for Oral Health Research, Virginia Commonwealth University School of Dentistry, Department of Oral and Craniofacial Molecular Biology, Richmond, VA 23298, USA; Department of Hematology, Oncology, and Palliative Care, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA; Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Brad
authors.initials: B
authors.lastname: Windle
authors.affiliation: University of Glasgow Institute of Infection, Immunology and Inflammation, Glasgow G12 8QQ, UK.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Donaldson
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Caffarel
authors.affiliation: University of Glasgow Institute of Infection, Immunology and Inflammation, Glasgow G12 8QQ, UK.
authors.forename: Edward S
authors.initials: ES
authors.lastname: Dornan
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Coleman
authors.affiliation: Institute of Molecular Cell and Systems Biology, University of Glasgow, Glasgow G12 8QQ, UK; Glasgow Polyomics, University of Glasgow, UK.
authors.forename: Pawel
authors.initials: P
authors.lastname: Herzyk
authors.affiliation: Department of Anatomy and Neurobiology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Henderson
authors.affiliation: VCU Philips Institute for Oral Health Research, Virginia Commonwealth University School of Dentistry, Department of Oral and Craniofacial Molecular Biology, Richmond, VA 23298, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: VCU Philips Institute for Oral Health Research, Virginia Commonwealth University School of Dentistry, Department of Oral and Craniofacial Molecular Biology, Richmond, VA 23298, USA; University of Glasgow Institute of Infection, Immunology and Inflammation, Glasgow G12 8QQ, UK; Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA. Electronic address: immorgan@vcu.edu.
authors.forename: Iain M
authors.initials: IM
authors.lastname: Morgan
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D015894:Genome, Human / Q000502:physiology*; D052162:Human papillomavirus 16 / Q000378:metabolism*; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012326:RNA Splicing / Q000187:drug effects*
chemical_list: D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral
keywords: Affymetrix; Cervical cancer; E2; Exon-array; Head and neck cancer; Host genome; Papillomavirus; Regulation; Splicing; Transcription