Determination of the Transforming Activities of Adenovirus Oncogenes

Abstract

Oncogenesis is a multistep process that ultimately leads to the demise of the organism. These steps can be mimicked in vitro by treatment of cultured animal cells with various oncogenic agents such as chemical carcinogens and oncogenic viruses. Oncogenes encoded by various DNA tumor viruses function as dominant oncogenes and can induce either immortalization of primary cells or oncogenic transformation of primary cells and certain established (immortalized) cell lines in vitro. Among the oncogenes of various DNA tumor viruses, the Ela oncogene of human adenoviruses is well-studied and serves as a prototypical transforming gene (reviewed inref. 1–3). Autonomous ectopic expression of the Ela gene can immortalize primary cells, thus conferring an ability to grow indefinitely in culture. Ela can also mediate oncogenic transformation in cooperation with cellular oncogenes such as the activated ras (T24 ras) oncogene (4) and other viral transforming genes such as adenovirus Elb and polyoma virus middle T antigen (5). In addition, Ela also exhibits an interesting tumor inhibitory activity by which it suppresses the metastatic potential of malignant tumor cells (reviewed in refs. 6 and7). Thus, theEla oncogene appears to offer an ideal tool to dissect the multistep process of oncogenesis.