A Role for HPV16 E5 in Cervical Carcinogenesis

• Published in: Cancer research (Chicago, Ill.) Vol. 70; no. 7; pp. 2924 - 2931
• Main Authors: MAUFORT, John P, SHAI, Anny, PITOT, Henry C, LAMBERT, Paul F
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.04.2010
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Cell Cycle - physiology; Cell Transformation, Viral - physiology; Estradiol - administration & dosage; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Humans; MAP Kinase Signaling System; Medical sciences; Mice; Mice, Transgenic; Oncogene Proteins, Viral - genetics; Oncogene Proteins, Viral - physiology; Oncogenes; Papillomavirus E7 Proteins - genetics; Papillomavirus E7 Proteins - physiology; Pharmacology. Drug treatments; Repressor Proteins - genetics; Repressor Proteins - physiology; Tumors; Uterine Cervical Neoplasms - chemically induced; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - virology; Papillomavirus; Virus; Human papillomavirus 16; Human papillomavirus; V-Onc gene; Papovaviridae; Malignant tumor; Carcinogenesis; Uterine cervix diseases; Cervical cancer; Cancer; Female genital diseases
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-09-3436

A subset of the mucosotropic human papillomaviruses (HPV), including HPV16, are etiologic agents for the vast majority of cervical cancers, other anogenital cancers, and a subset of head and neck squamous cell carcinomas. HPV16 encodes three oncogenes: E5, E6, and E7. Although E6 and E7 have been well-studied and clearly shown to be important contributors to these cancers, less is known about E5. In this study, we used E5 transgenic mice to investigate the role of E5 in cervical cancer. When treated for 6 months with estrogen, a cofactor for cervical carcinogenesis, E5 transgenic mice developed more severe neoplastic cervical disease than similarly treated nontransgenic mice, although no frank cancers were detected. In addition, E5 when combined with either E6 or E7 induced more severe neoplastic disease than seen in mice expressing only one viral oncogene. Prolonged treatment of E5 transgenic mice with exogenous estrogen uncovered an ability of E5 to cause frank cancer. These data indicate that E5 acts as an oncogene in the reproductive tracts of female mice.