title: HPV16 E6 regulates annexin 1 (ANXA1) protein expression in cervical carcinoma cell lines.
abstract: Annexin 1 (ANXA1) is a substrate for E6AP mediated ubiquitylation. It has been hypothesized that HPV 16 E6 protein redirects E6AP away from ANXA1, increasing its stability and possibly contributing to viral pathogenesis. We analyzed ANXA1 expression in HPV-positive and negative cervical carcinoma-derived cells, in cells expressing HPV-16 oncogenes and in cells transduced with shRNA targeting E6AP. We observed that ANXA1 protein expression increased in HPV-16-positive tumor cells, in keratinocytes expressing HPV-16 E6wt (wild-type) or E6/E7 and C33 cells expressing HPV-16 E6wt. ANXA1 protein expression decreased in cells transfected with E6 Dicer-substrate RNAs (DsiRNA) and C33 cells cotransduced with HPV-16 E6wt and E6AP shRNA. Moreover, colony number and proliferation rate decreased in HPV16-positive cells transduced with ANXA1 shRNA. We observed that in cells infected with HPV16, the E6 binds to E6AP to degrade p53 and upregulate ANXA1. We suggest that ANXA1 may play a role in HPV-mediated carcinogenesis.
authors.affiliation: Department of Biology, Institute of Bioscience, Language and Exact Science, São Paulo State University, São Jose do Rio Preto, Brazil.
authors.forename: Marilia Freitas
authors.initials: MF
authors.lastname: Calmon
authors.affiliation: Molecular Biology Laboratory, Centre for Translational Research in Oncology, Instituto do Câncer do Estado de São Paulo (ICESP), São Paulo, Brazil.
authors.forename: Laura
authors.initials: L
authors.lastname: Sichero
authors.affiliation: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo., São Paulo, Brazil.
authors.forename: Enrique
authors.initials: E
authors.lastname: Boccardo
authors.affiliation: Department of Radiology and Oncology, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Luisa Lina
authors.initials: LL
authors.lastname: Villa
authors.affiliation: Department of Biology, Institute of Bioscience, Language and Exact Science, São Paulo State University, São Jose do Rio Preto, Brazil. Electronic address: rahalp@yahoo.com.br.
authors.forename: Paula
authors.initials: P
authors.lastname: Rahal
mesh_terms: D017305:Annexin A1 / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D052162:Human papillomavirus 16 / Q000502:physiology; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000150:complications / Q000821:virology; D059748:Proteolysis; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000209:etiology* / Q000378:metabolism*
chemical_list: D017305:Annexin A1; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53
keywords: ANXA1; Cervical cell lines; E6; HPV16; Keratinocytes; P53