No abstract

We investigated the expression of cellular sequences c-rasKi and c-fms, which are homologous to the oncogenes of Kirsten rat sarcoma virus and the McDonough strain offeline sarcoma virus, during murine development and in a variety of mouse tissues. The c-rasKi gene was found to be transcribed into two mRNA species of approximately 2.0 and 4.4 kilobases, whereas a single c-fms-related transcript of approximately 3.7 kilobases was identified. The c-rasKi gene appeared to be expressed ubiquitously, since similar levels of transcripts were observed in embryos, fetuses, extraembryonal structures, and a variety of postnatal tissues. In contrast, significant expression of c-fms was found to be confined to the placenta and extraembryonal membranes (i.e., combined yolk sac and amnion). The concentration of c-fms transcripts in the placenta increased approximately 15-fold (relative to day-7 to day-9 conceptuses) during development before reaching a plateau at day 14 to 15 of gestation. The time course of cfms expression in the extraembryonal membranes appeared to parallel the stagespecific pattern observed in the placenta. The level of c-fms transcripts in the extraembryonal tissues reached a level which was approximately 20-to 50-fold greater than that in the fetus. These findings suggest that the c-fms gene product may play a role in differentiation of extraembryonal structures or in transport processes occurring in these tissues. Our results indicate that the c-onc genes analyzed in the present study exert essentially different functions durin-g mouse development.The acutely oncogenic retroviruses contain sequences in their genomes which are required for induction of neoplasia in vivo and for morphological and malignant transformation of cultured cells in vitro (3, 50). These sequences, termed viral oncogenes (v-onc), apparently originated from the normal vertebrate genome (3,50). The precise mechanism of acquisition of these cellular sequences remains obscure, but it presumably involves recombination between the genome of a replication-competent retrovirus and the host genome (3, 50). To date, 16 different cellular homologs of retroviral oncogenes have been identified

Cellular genes containing nucleotide sequences homologous to retroviral oncogenes (v-onc) have been identified in the genomes of a variety of species of both the vertebrate and invertebrate phyla. Expression of such genes, termed c-onc genes, has been shown to be tissue-specific in chickens and mice and to be modulated during murine development and differentiation of human haematopoietic cells. We report here that the level of the c-fos gene transcripts is 100-fold greater in human term fetal membranes than in other normal human tissues and cells. These levels of c-fos expression in human amniotic and chorionic cells are close to the level of v-fos expression that results in the induction of osteosarcomas in mice and transformation of fibroblasts in vitro. This observation suggests that the induction of neoplastic transformation by the FBJ murine osteosarcoma virus may require the expression of the fos gene product at high levels in an inappropriate cell type. In contrast, the human c-fms gene is expressed at high levels specifically in term placenta and trophoblastic cells. The tissue and cell type-specific patterns of c-fos and c-fms expression suggest that the physiological function of the c-fos and c-fms encoded proteins may be associated with those embryo-derived cells whose primary functions are protection and nourishment of the human fetus.

h n S. H o l m e s , L i -H s i e n Rin, J o a n n e M. T r e m b l a y , a n d R o b e r t K. Zeldin ( C o m p i l e d a n d e d i t e d b y [Barbara S.K. S t a n l e y ) fir at WESTERN MICHIGAN UNIVERSITY on June 5, 2016 gct.sagepub.com Downloaded from

We investigated the expression of cellular sequences c-rasKi and c-fms, which are homologous to the oncogenes of Kirsten rat sarcoma virus and the McDonough strain of feline sarcoma virus, during murine development and in a variety of mouse tissues. The c-rasKi gene was found to be transcribed into two mRNA species of approximately 2.0 and 4.4 kilobases, whereas a single c-fms-related transcript of approximately 3.7 kilobases was identified. The c-rasKi gene appeared to be expressed ubiquitously, since similar levels of transcripts were observed in embryos, fetuses, extraembryonal structures, and a variety of postnatal tissues. In contrast, significant expression of c-fms was found to be confined to the placenta and extraembryonal membranes (i.e., combined yolk sac and amnion). The concentration of c-fms transcripts in the placenta increased approximately 15-fold (relative to day-7 to day-9 conceptuses) during development before reaching a plateau at day 14 to 15 of gestation. The time course of cfms expression in the extraembryonal membranes appeared to parallel the stage-specific pattern observed in the placenta. The level of c-fms transcripts in the extraembryonal tissues reached a level which was approximately 20- to 50-fold greater than that in the fetus. These findings suggest that the c-fms gene product may play a role in differentiation of extraembryonal structures or in transport processes occurring in these tissues. Our results indicate that the c-onc genes analyzed in the present study exert essentially different functions during mouse development.