Pulmonary and Nasal Adenocarcinomas Induced by Ovine P-Retroviruses

摘要

Lung cancer is the leading cause of cancer-related morbidity and mortality worldwide. Although the majority of lung cancers are associated with tobacco smoking, a certain percentage of lung cancer patients are not associated with tobacco smoking, suggesting that some other factors may be involved, including chromosomal aberrations, gene mutations, DNA methylation, or oncogenic viruses. As a useful animal model for human pulmonary carcinogenesis, ovine pulmonary adenocarcinoma (OPA) has been investigated. OPA is a transmissible and spontaneous lung tumor of sheep that has similarities to some forms of human lung adenocarcinoma. The etiologic agent of OPA is jaagsiekte sheep retro virus (JSRV), which is unique among retroviruses with a specific tropism for alveolar type II pneumocytes and bronchiolar Clara cells of the lung due to the specificity of its promoter/enhancer sequences. With regard to OPA tumorigenesis the JSRV envelope (Env) protein functions as an oncoprotein, since it can morphologically transform fibroblast and epithelial cells in vitro and induce lung cancer in sheep and mice. Similarly, enzootic nasal tumor virus (ENTV), closely related to JSRV, is the causative agent of enzootic nasal adenocarcinoma (ENA) in sheep and goats, and the ENTV Env also functions as an oncoprotein. The mechanisms of signal transduction induced by the two Env proteins are currently being investigated. We will summarize the current progress on ovine p-retrovirus Env-mediated tumorigenesis and discuss their relevance to human cancer.