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 anal
ogies to some forms of human adenocarcinoma. The etiologic agent of OPA, ja
agsiekte 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 adenocarcino
ma. Expression of the JSRV envelope protein is sufficient to induce cell tr
ansformation in vitro, possibly via the activation of the phosphatidylinosi
tol 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 b
asic 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 similariti
es between OPA and some forms of human lung adenocarcinoma. The possibility
of a viral etiology for the latter will be evaluated in this review.