Oncogene Requirements for Tumorigenicity: Cooperative Effects between Retroviral Oncogenes

Abstract

Several independent lines of evidence have established an association between the induction of a malignant phenotype and the expression of specific pairs of oncogenes. The first line of support comes from investigations involving the tumorigenic conversion of primary rodent cells by complementary pairs of cotransfected oncogenes (see reviews by Land et al. 1983b; Weinberg 1985). Second, the genetic analysis of cell lines derived from neoplastic tissue has revealed that some contain alterations in at least two cellular genes termed proto-oncogenes (reviewed in Bishop 1987). Such results have suggested that multiple genetic mutations are required for tumor formation, a notion based on tumor induction studies involving chemical carcinogens (see review by Sukumar this volume). Third, a variety of interactions between retroviral oncogenes, denoted as v-oncs, has been recently described in different types of retrovirus-transformed cells. These interaction are manifested both in vivo and in vitro and result in tumor induction (synergy), tumor augmentation (enhancement), cell proliferation in the absence of specialized culture conditions, or growth factor-independent cell proliferation. In addition to this body of evidence, a unique group of avian retroviruses exists in which each virus encodes pairs of cooperating oncogenes (reviewed in Graf and Beug 1983; Kahn et al. 1986b). The existence of such naturally occurring viruses implies that oncogene complementation represents one process of rapid tumor formation in nature and is not merely a novel laboratory phenomenon.