title: Inhibitors of differentiation-1 promotes nitrosopyrrolidine-induced transformation of HPV 16-immortalized cervical epithelial cell.
abstract: Our previous study implied a correlation between inhibitors of differentiation-1 (Id-1) and cervical cancer development. However, how Id-1 contributes to cervical carcinogenesis is unknown. In the present study, we used an in vitro transformation model to investigate the role of Id-1 in the transformation of cervical cells. Human papillomavirus (HPV)-immortalized cervical epithelial cells (H8) were successfully transformed by exposure to the carcinogen N-nitrosopyrrolidine (NPYR). The expression of both Id-1 RNA and protein was significantly increased in transformed H8 cells, suggesting a possible role of Id-1 in cervical cell transformation. Ectopic expression of Id-1 in H8 cells potentiated NPYR-induced cell transformation. In contrast, silencing of Id-1 suppressed NPYR-induced H8 cell transformation. In addition, the expression of HPV E6 and E7 oncoproteins was upregulated while that of the tumor suppressors p53 and pRb was suppressed after H8 cell transformation. Our results suggest that Id-1 plays an oncogenic role in HPV-related cervical carcinogenesis, which sheds light on cervical cancer development mechanisms and implies that Id-1 is a potential target for cervical cancer prevention and therapy.
authors.affiliation: Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, China; Laboratory of Biomedical Ultrasonics/Gynecological Oncology Laboratory, West China Second Hospital, Sichuan University, Chengdu, China.
authors.forename: Lingxia
authors.initials: L
authors.lastname: Xie
authors.forename: Jinke
authors.initials: J
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Bao
authors.initials: B
authors.lastname: Liu
authors.forename: Xue
authors.initials: X
authors.lastname: Peng
authors.forename: Yong
authors.initials: Y
authors.lastname: Lin
authors.forename: Wenming
authors.initials: W
authors.lastname: Xu
authors.forename: Lina
authors.initials: L
authors.lastname: Hu
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology*; D004847:Epithelial Cells / Q000187:drug effects / Q000821:virology; D005260:Female; D052162:Human papillomavirus 16; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009242:N-Nitrosopyrrolidine / Q000633:toxicity; D009368:Neoplasm Transplantation; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins / Q000096:biosynthesis / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering; D012097:Repressor Proteins / Q000096:biosynthesis / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000821:virology*
chemical_list: D002273:Carcinogens; C068651:E6 protein, Human papillomavirus type 16; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; C059731:oncogene protein E7, Human papillomavirus type 16; D009242:N-Nitrosopyrrolidine
keywords: Carcinogenesis; cervical cancer; human papillomavirus; inhibitors of differentiation-1; transformation