title: Effect of human papillomavirus 16 oncoproteins on oncostatin M upregulation in oral squamous cell carcinoma.
abstract: Human papillomavirus (HPV) infection modulates several host cytokines contributing to cancer development. Oncostatin M (OSM), an IL-6 family cytokine, acts to promote cell senescence and inhibit growth. Its dysregulation promotes cell survival, cell proliferation and metastasis in various malignancies. The effect of HPV on OSM dysregulation has not been investigated. To elucidate this, immunohistochemistry was used on formalin-fixed, paraffin-embedded oral squamous cell carcinoma (OSCC) tissues: HPV-positive (50) and HPV-negative (50) cases. Immortalized human cervical keratinocytes expressing HPV16E6 (HCK1T, Tet-On system) were used to demonstrate the role of HPV16E6 in OSM expression. In addition, a vector containing HPV16E6/E7 was transiently transfected into oral cancer cell lines. Cell viability, cell-cycle progression and cell migration were evaluated using flow cytometry and a wound healing assay, respectively. The results showed various intensities of OSM expression in OSCC. Interestingly, the median percentages of strongly stained cells were significantly higher in HPV-positive OSCCs than in HPV-negative OSCCs. To explore the role of HPV oncoproteins on OSM expression, the expression of HPV16E6 in the HCK1T Tet-On condition was induced by doxycycline and HPV16E6 was found to significantly upregulate levels of OSM mRNA and protein, with concomitant upregulation of c-Myc. In addition, the levels of OSM mRNA and protein in E6/E7 transiently transfected oral cancer cells also gradually increased in a time-dependent manner and these transfected cells showed greater viability and higher migration rates and cell-cycle progression than controls. This result demonstrates that HPV16 oncoproteins upregulate OSM and play an important role to promote OSCC development.
authors.affiliation: Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.|HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Jureeporn
authors.initials: J
authors.lastname: Chuerduangphui
authors.affiliation: Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.|HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Chamsai
authors.initials: C
authors.lastname: Pientong
authors.affiliation: Department of Oral Diagnosis, Faculty of Dentistry, Khon Kaen University, Khon Kaen, Thailand.|Research Group of Chronic Inflammatory Oral Diseases and Systemic Diseases Associated with Oral Health, Faculty of Dentistry, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Ponlatham
authors.initials: P
authors.lastname: Chaiyarit
authors.affiliation: Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.|HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Natcha
authors.initials: N
authors.lastname: Patarapadungkit
authors.affiliation: Anatomical Pathology Unit, Khon Kaen Hospital, Khon Kaen, Thailand.|HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Apinya
authors.initials: A
authors.lastname: Chotiyano
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Bunkerd
authors.initials: B
authors.lastname: Kongyingyoes
authors.affiliation: Department of Epidemiology, Faculty of Public Health, Khon Kaen University, Khon Kaen, Thailand.|HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Supannee
authors.initials: S
authors.lastname: Promthet
authors.affiliation: Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.|HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Piyawut
authors.initials: P
authors.lastname: Swangphon
authors.affiliation: Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.|HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Weerayut
authors.initials: W
authors.lastname: Wongjampa
authors.affiliation: Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. tipeka@kku.ac.th.|HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand. tipeka@kku.ac.th.
authors.forename: Tipaya
authors.initials: T
authors.lastname: Ekalaksananan
mesh_terms: D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000821:virology*; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000821:virology*; D052162:Human papillomavirus 16; D006801:Humans; D007150:Immunohistochemistry; D009062:Mouth Neoplasms / Q000378:metabolism / Q000821:virology*; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D053683:Oncostatin M / Q000096:biosynthesis*; D030361:Papillomavirus Infections / Q000378:metabolism*; D000077195:Squamous Cell Carcinoma of Head and Neck; D046888:Tissue Array Analysis; D015854:Up-Regulation
chemical_list: D009856:Oncogene Proteins, Viral; D053683:Oncostatin M
keywords: Human papillomavirus; Interleukin-6; Oncostatin M; Oral squamous cell carcinoma; STAT3; c-Myc