title: IL-10 expression is regulated by HPV E2 protein in cervical cancer cells.
abstract: It has been found that certain cytokines (IL-4, IL-10 and TGF-β1) are highly expressed locally in biopsies from patients with premalignant lesions and cervical cancer, and may induce a local immune-suppression state. In particular, IL-10 is highly expressed in tumor cells and its expression is directly proportional to the development of HPV-positive cervical cancer, suggesting an important role of HPV proteins in the expression of IL-10. In fact, we demonstrated that E6 and E7 HPV proteins regulate TGF-β1 gene expression in cervical cancer cells. Here, we found by band shifting analysis that the HPV E2 protein binds to the regulatory region of the human IL-10 gene (-2054 nt) and induces high promoter activity in epithelial cells. Additionally, cervical cancer cells transfected to express the HPV E2 protein induce elevated levels of IL-10 mRNA in human papillomavirus-infected cells. The elevated expression of IL-10 may allow for virus persistency, the transformation of cervical epithelial cells, and consequently cancer development.
authors.affiliation: Division of Chronic Infections and Cancer, CISEI, National Institute of Public Heath, Morelos 62100, Mexico.
authors.forename: V H
authors.initials: VH
authors.lastname: Bermúdez-Morales
authors.forename: O
authors.initials: O
authors.lastname: Peralta-Zaragoza
authors.forename: J M
authors.initials: JM
authors.lastname: Alcocer-González
authors.forename: J
authors.initials: J
authors.lastname: Moreno
authors.forename: V
authors.initials: V
authors.lastname: Madrid-Marina
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; C508609:IL10 protein, human; D009856:Oncogene Proteins, Viral; D016753:Interleukin-10