Increased Growth of a Newly Established Mouse Epithelial Cell Line Transformed with HPV-16 E7 in Diabetic Mice

• Published in: PloS one Vol. 11; no. 10; p. e0164490
• Main Authors: He, Lan, Law, Priscilla T Y, Boon, Siaw Shi, Zhang, Chuqing, Ho, Wendy C S, Banks, Lawrence, Wong, C K, Chan, Juliana C N, Chan, Paul K S
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17.10.2016; Public Library of Science (PLoS)
• Subjects: Analysis; Animals; Anogenital; Biology and life sciences; Cancer; Cancer research; Carcinogenesis; Carcinogens; Cell Line, Transformed; Cell Proliferation; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cervical cancer; Cervix; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - pathology; Environmental risk; Epidemiology; Epithelial cells; Epithelial Cells - cytology; Epithelial Cells - metabolism; Epithelial Cells - transplantation; Ethics; Growth; Health aspects; Health risks; Health sciences; Hospitals; House mouse; Human papillomavirus; Human papillomavirus 16 - genetics; Human papillomavirus 16 - metabolism; Laboratory animals; Male; Medical research; Medical screening; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Mice, Nude; Neoplasms - etiology; Neoplasms - pathology; Oncogene Proteins, Viral - genetics; Papillomaviridae; Papillomavirus E7 Proteins - genetics; Papillomavirus E7 Proteins - metabolism; Papillomavirus infections; Pathogenicity; Pathogens; Proteins; Research and Analysis Methods; Retina; Retinoblastoma; Retinoblastoma protein; Risk analysis; Risk factors; RNA, Messenger - metabolism; Statistics; Transplantation, Homologous; Tumorigenesis; Type 2 diabetes; Xenografts; Xenotransplantation; Hong Kong China; United Kingdom > UK; United States > US; Wales
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0164490

Epidemiological evidence supports that infection with high-risk types of human papillomavirus (HPV) can interact with host and environmental risk factors to contribute to the development of cervical, oropharyngeal, and other anogenital cancers. In this study, we established a mouse epithelial cancer cell line, designated as Chinese University Papillomavirus-1 (CUP-1), from C57BL/KsJ mice through persistent expression of HPV-16 E7 oncogene. After continuous culturing of up to 200 days with over 60 passages, we showed that CUP-1 became an immortalized and transformed epithelial cell line with continuous E7 expression and persistent reduction of retinoblastoma protein (a known target of E7). This model allowed in-vivo study of interaction between HPV and co-factors of tumorigenesis in syngeneic mice. Diabetes has been shown to increase HPV pathogenicity in different pathological context. Herein, with this newly-established cell line, we uncovered that diabetes promoted CUP-1 xenograft growth in syngeneic db/db mice. In sum, we successfully established a HPV-16 E7 transformed mouse epithelial cell line, which allowed subsequent studies of co-factors in multistep HPV carcinogenesis in an immunocompetent host. More importantly, this study is the very first to demonstrate the promoting effect of diabetes on HPV-associated carcinogenesis in vivo, implicating the importance of cancer surveillance in diabetic environment.