title: Establishment of two immortalized nasopharyngeal epithelial cell lines using SV40 large T and HPV16E6/E7 viral oncogenes.
abstract: Nasopharyngeal carcinoma (NPC) is a common cancer in Southeast Asia, especially in southern China. One of the most striking features of this disease is its close relationship with Epstein-Barr Virus (EBV). However, to date there is no direct study on the mechanisms involved in the role of EBV in the tumorigenesis of NPC, largely due to lack of an experimental model. Available hypotheses on the association between EBV and NPC are generated from non-nasopharyngeal epithelial cell systems such as human keratinocytes or mouse epithelial cells, which may not truly represent the biological properties of nasopharyngeal epithelial (NP) cells. In this study, we report the establishment of two immortalized NP cell lines, NP69SV40T and NP39E6/E7, using SV40T and HPV16E6/E7 oncogenes. We found that NP60SV40T and NP39E6/E7 cell lines not only maintained many characteristics of normal NP cells (i.e. keratin profile and responsive to TGFbeta inhibition) but also highly responsive to one of the EBV encoded genes, LMP1. Comparative genome hybridization (CGH) analysis showed that these two cell lines contained multiple genetic alterations, some of which have been described in NPC. The immortalized NP cell lines are non-tumorigenic and exhibit anchorage-dependent growth. These cell lines may provide a possible cell model system for studying the mechanisms involved in the tumorigenesis of NPC.
authors.affiliation: Department of Anatomy, Faculty of Medicine, University of Hong Kong, New Medical Complex, 1st Floor, Laboratory Block, 21 Sassoon Road, Pokfulam, Hong Kong, China. gswtsao@hkucc.hku.hk
authors.forename: Sai Wah
authors.initials: SW
authors.lastname: Tsao
authors.forename: Xianghong
authors.initials: X
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Yuk Chun
authors.initials: YC
authors.lastname: Cheung
authors.forename: Huichen
authors.initials: H
authors.lastname: Feng
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zheng
authors.forename: Natalie
authors.initials: N
authors.lastname: Wong
authors.forename: P W
authors.initials: PW
authors.lastname: Yuen
authors.forename: Angela K F
authors.initials: AK
authors.lastname: Lo
authors.forename: Y C
authors.initials: YC
authors.lastname: Wong
authors.forename: D P
authors.initials: DP
authors.lastname: Huang
mesh_terms: D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D002455:Cell Division; D002461:Cell Line, Transformed; D002877:Chromosomes, Human / Q000235:genetics; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005814:Genes, Viral; D004854:Herpesvirus 4, Human / Q000472:pathogenicity; D006801:Humans; D008954:Models, Biological; D009303:Nasopharyngeal Neoplasms / Q000209:etiology; D009305:Nasopharynx / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D009856:Oncogene Proteins, Viral / Q000235:genetics; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D013539:Simian virus 40 / Q000235:genetics; D019098:Telomerase / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D014763:Viral Matrix Proteins / Q000378:metabolism
chemical_list: D000952:Antigens, Polyomavirus Transforming; C068651:E6 protein, Human papillomavirus type 16; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014763:Viral Matrix Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D019098:Telomerase