Avian leukosis virus-induced tumors have common proviral integration sites and synthesize discrete new RNAs: oncogenesis by promoter insertion

• Published in: Cell Vol. 23; no. 2; p. 323
• Main Authors: Neel, B G, Hayward, W S, Robinson, H L, Fang, J, Astrin, S M
• Format: Journal Article
• Language: English
• Published: United States 01-02-1981
• Subjects: Animals; Avian Leukosis - etiology; Avian Leukosis Virus - genetics; Cell Line; Cell Transformation, Neoplastic; Chickens; Genes, Viral; Lymphoma - etiology; Models, Genetic; Operon; Recombination, Genetic; RNA, Neoplasm - biosynthesis
• ISSN: 0092-8674
• DOI: 10.1016/0092-8674(81)90128-8

Unlike other RNA tumor viruses, avian leukosis viruses (which cause lymphomas and occasionally other neoplasms) lack discrete "transforming genes". We have analyzed the virus-related DNA and RNA of avian leukosis virus (ALV)-induced tumors in an attempt to gain insight into the mechanism of ALV oncogenesis. Our results show that viral gene products are not required for maintenance of neoplastic transformation. Primary and metastatic tumors are clonal and thus presumably derived from a single infected cell. Most importantly, tumors from different birds have integration sites in common. Tumor cells synthesize discrete new poly(A) RNAs consisting of viral sequences covalently linked to cellular sequences. These RNA species are expressed at high levels in tumor cells. Our results suggest that in lymphoid tumors, an ALV provirus is integrated adjacent to a specific cellular gene, and the insertion of the viral promoter adjacent to this gene results in its enhanced expression, leading to neoplasia. These results have potentially important implications for the mechanism of non-viral carcinogenesis.