Cellular sequences related to three new onc genes of avian sarcoma virus (fps, yes, and ros) and their expression in normal and transformed cells.

Abstract

Two onc genes of avian sarcoma viruses unrelated to the src gene have recently been identified: fps of Fujinami sarcoma virus/PRCII/UR1 and yes of Y73/Esh sarcoma virus. In the first part of this study we demonstrated that UR2, the most recently isolated avian sarcoma virus, contains in its genome a unique sequence, ros, nonhomologous to src, fps, and yes sequences or to transforming genes of avian acute leukemia viruses. Using cDNAs specific to the inserts of avian sarcoma virus genomes, we examined the existence and the transcription of cellular nucleotide sequences related to the three new onc genes of avian sarcoma virus (fps, yes and ros) in various cells. The progenitor cellular sequences for these onc genes (c-onc) were present in uninfected chicken DNA in one or few copies per haploid genome. These c-onc sequences were detectable in cellular DNA of a wide variety of vertebrates, and the homology between viral and cellular onc was inversely related to the phylogenetic distance of animal species. The pattern of expression of these c-onc genes in different tissues of chickens was found to be unique to each gene. The expression of c-fps and c-ros genes was generally repressed in many tissues, but c-fps was expressed at higher levels in bone marrow (2.5 copies per cell) and lung (1.1 copies per cell), whereas c-ros was mainly transcribed in kidney (2.5 copies per cell). On the other hand, c-yes transcripts were easily detectable in all tissues analyzed and were found at high levels in kidney (26 copies per cell). These c-onc expressions were unaffected by infection with avian sarcoma viruses that contained other onc genes. In a few cultures of chicken and quail transformed cells derived from tumors induced by chemical carcinogens, we found that the levels of transcription of the four c-onc genes remained unaltered, compared with that in normal tissues.