Retrovirus-Induced Ovine Pulmonary Adenocarcinoma, an Animal Model for Lung Cancer

Studies on the molecular mechanisms of transformation of retrovirus-induced neoplasms in domestic and laboratory animal species have provided insights into the genetic basis of cancer. Ovine pulmonary adenocarcinoma (OPA) is a retrovirus-induced spontaneous lung tumor of sheep that has striking analogies to some forms of human adenocarcinoma. The etiologic agent of OPA, jaagsiekte sheep retrovirus (JSRV), is unique among retroviruses for having a specific tropism for the differentiated epithelial cells of the lung, and it is the only virus known to cause a naturally occurring lung adenocarcinoma. Expression of the JSRV envelope protein is sufficient to induce cell transformation in vitro, possibly via the activation of the phosphatidylinositol 3-kinase/Akt-signaling pathway mediated by the cytoplasmic tail of the transmembrane protein. The aim of this review is to draw the attention of basic and clinical scientists engaged in lung cancer research to this unique animal model, to explore the possible use of OPA as a tool to investigate the mechanisms of pulmonary carcinogenesis, and to underline the similarities between OPA and some forms of human lung adenocarcinoma. The possibility of a viral etiology for the latter will be evaluated in this review.