Alfred P. Sloan prize. Towards a biochemical description of malignant transformation: Identification and functional characterization of the rous sarcoma virus transforming gene product

Abstract

published his seminal work that I showed that a malignant sarcoma of chickens could be transmitted by a cell-free filtrate. Experiments with this virus or closely related descendents have continued to yield exciting new findings to this day. Although numerous papers have been published describing experiments on what came to be known as the Rous sarcoma virus (RSV), current modern molecular studies of viruses as agents that cause cancer began with two additional key developments. The first development was the demonstration by Manaker and Group;' in 1956 and by Temin and Rubin'" in 1958 that RSV could be grown to high titers in cultured chicken fibroblasts and could morphologically transform these cells; the number of transformed cells could be used to quantitate the amount of virus. The second development was the accumulation of genetic evidence that RSV camed a transforming gene, a gene that, when expressed, was responsible for malignant transformation. This gene was defined by the isolation and analysis of several mutants of RSV which had an altered capacity to transform cells. There are two classes of RSV mutants: (1) conditional mutants, which are temperature-sensitive for transformation; and (2) nonconditional mutants, which are inactive for transformation under all conditions. The first RSV temperature-sensitive mutants were isolated by Toyoshima andVogt' in 1969 and Martin3 in 1970. Evidence published by Wang and coworkers4 in 1973 suggested that the nonconditional RSV mutants had deletions of the transforming gene. Biochemical studies revealed that the temperature-sensitive mutations occurred in the same region of the genome that was deleted in the nonconditional mutants.This lecture is dedicated to the memory of Renzo Rendi, in appreciation of his courage, interest, and suggestions.