title: GSK3β mediates the carcinogenic effect of HPV16 in cervical cancer.
abstract: Cervical cancer is one of the most prevalent and fatal cancers among women and infection of the human papillomavirus (HPV) is the most important risk factor. This study investigated how HPV16 regulated GSK3β expression and function to promote cervical cancers. The expression of GSK3β was analyzed by quantitative PCR and western blot. The proliferation, invasion, and clonogenic survival of cells with different E6/E7 levels were measured by MTT, transwell invasion assays, and soft agar colony-forming assays, respectively. The levels of GSK3β were correlated with the copy numbers and expression levels of HPV16 E6/E7 genes. HPV16 E6/E7 genes regulated GSK3β transcription through an element located in the promoter 85 and 250 base pairs upstream of the transcription start site. The abilities of cell proliferation, invasion, and clonogenic survival were increased in C33A cells by ectopic HPV16 E6/E7 and decreased in CaSki cells by knocking down HPV16 E6/E7 levels. Meanwhile, LiCl increased GSK3β transcript levels and the proliferation of CaSki cells in a HPV16-dependent manner. These data indicated that GSK3β may participated in HPV16 mediated deregulation of wnt/β-catenin and other signaling pathways promoting the progression and invasion of cervical cancers.
authors.affiliation: Department of Dermatology, Fourth Military Medical University, China.
authors.forename: Cuiling
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Dermatology, Fourth Military Medical University, China.
authors.forename: Chenglong
authors.initials: C
authors.lastname: Zeng
authors.affiliation: Department of Dermatology, Fourth Military Medical University, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Jin
authors.affiliation: Department of Dermatology, Fourth Military Medical University, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Dermatology, Fourth Military Medical University, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University, China.
authors.forename: Liangfeng
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D002472:Cell Transformation, Viral; D004279:DNA, Viral; D005260:Female; D018628:Gene Dosage; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D052162:Human papillomavirus 16 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000378:metabolism; D030361:Papillomavirus Infections / Q000150:complications* / Q000821:virology; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D002583:Uterine Cervical Neoplasms / Q000209:etiology* / Q000378:metabolism*
chemical_list: D004279:DNA, Viral; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3