Jaagsiekte sheep retrovirus (JSRV) is the causative agent of contagious lung cancer of sheep called ovine pulmonary adenocarcinoma (OPA), in which differentiated secretory epithelial cells are specifically transformed. OPA strongly resembles human bronchioloalveolar caricinoma (BAC), which accounts for about 1-10% of all human lung cancers with etiology currently unknown. Recent studies show that the envelope (Env) glycoprotein of JSRV can transform cultured rodent fibroblasts, suggesting an essential role of this viral structural protein in ovine tumorigenesis. My thesis projects are focusing on mapping the domains or specific amino acid residues in JSRV Env protein that are responsible for oncogenesis, and investigating the molecular mechanisms of cell transformation. Preliminary data indicate: (1) the cytoplasmic domain, in particular, the tyrosine residue of YXXM motif within this domain, plays a pivotal role in cell transformation; (2) PKB/Akt is activated in JSRV Env transformed cells compared to the nontransformed cells; (3) Phosphatidylinositol-3 kinase (PI3-K) specific inhibitors suppress cell transformation and reverse the transformed phenotypes by JSRV Env; (4) Human Hyaluronidase 2 (HYAL2), the cellular receptor for JSRV, acts as a tumor suppressor in suppressing the JSRV Env induced transformation and reverting the transformed phenotypes, possibly through a direct interaction with JSRV surface protein (SU). Characterization of oncogenic properties of JSRV may provide important insights into our understanding the etiology and pathogenesis of human BAC.