title: HPV16E6-dependent c-fos expression contributes to AP-1 complex formation in SiHa cells.
abstract: To date, the major role of HPV16E6 in cancer has been considered to be its ability to inhibit the p53 tumor-suppressor protein, thereby thwarting p53-mediated cytotoxic responses to cellular stress signals. Here, we show that HPV16E6-dependent c-fos oncogenic protein expression contributes to AP-1 complex formation under oxidative stress in SiHa cells (HPV16-positive squamous cell carcinoma of the cervix). In addition, we examined the role of HPV16E6 in TGF-α-induced c-fos expression and found that the c-fos protein expression induced by TGF-α is HPV16E6 dependent. Thus, our results provide the first evidence that HPV16E6 contributes to AP-1 complex formation after both ligand-dependent and independent EGFR activation, suggesting a new therapeutic approach to the treatment of HPV-associated tumors.
authors.affiliation: Department of Clinical Neuroscience Oral and Maxillofacial Functional Rehabilitation, University of Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan.
authors.forename: Feixin
authors.initials: F
authors.lastname: Liang
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Kina
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takemoto
authors.forename: Akira
authors.initials: A
authors.lastname: Matayoshi
authors.forename: Thongsavanh
authors.initials: T
authors.lastname: Phonaphonh
authors.forename: Nao
authors.initials: N
authors.lastname: Sunagawa
authors.forename: Keiichi
authors.initials: K
authors.lastname: Arakaki
authors.forename: Akira
authors.initials: A
authors.lastname: Arasaki
authors.forename: Hai
authors.initials: H
authors.lastname: Kuang
authors.forename: Hajime
authors.initials: H
authors.lastname: Sunakawa
mesh_terms: D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D016760:Proto-Oncogene Proteins c-fos; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D018808:Transcription Factor AP-1; D016211:Transforming Growth Factor alpha