Does the Large T Protein of Polyoma Virus Regulate the Expression of the Cellular myc Gene?

Abstract

Upon expression of the large T protein of polyoma virus from genes encoding only this protein (plt genes: intron-less gene in pPyLT1 plasmid) (Tyndall et al., 1981), hrt mutant NG18 (Schaffhausen et al., 1978)), changes were observed in the behaviour in culture of rodent embryo fibroblast cells in primary cultures (REF) (Rassoulzadegan et al., 1982, 1983): the cells grew in culture for an unlimited number of generations (“immortalization”) and grew in the presence of low concentrations of serum (below 1% newborn calf serum). They maintained, however, the extended morphology, the low saturation density and the anchorage dependency characteristic of the normal fibroblast. Unlike the original REF- cells, these “immortalized” lines could be transformed by transfer of the polyoma virus gene encoding only the middle T protein (pmt gene: plasmid pPyMT1, Treisman et al., 1981), thus demonstrating a two-step process in tumorigenic transformation. A similar two-step mechanism was suggested by Land et al. (1983) for the myc and ras families of cellular oncogenes: expression either of the polyoma plt or of v-myc and rearranged c-myc genes allowed transformation of REF cells with activated forms of the ras genes. These results suggest that both genes exert similar function (s) at an early step of the transformation of REF cells in culture. This class of oncogenes also includes the E1a genes of adenovirus 2, required for transformation by the E1b genes of the same virus and which can also cooperate with a ras oncogene in REF transformation (Van den Elsen et al., 1982, Ruley, 1983).