Multiplicity of Cell Response to a Murine Erythroblastosis Virus1

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

show abstract

“…HaSV and KiSV cause erythroblastosis, extrathymic lymphomas, and sarcomas in rodents (25,27 Fig. 1 and 2 and unpublished data).…”

mentioning

confidence: 87%

Transcription of c-onc genes c-rasKi and c-fms during mouse development.

Müller¹,

Slamon²,

Adamson³

et al. 1983

Mol. Cell. Biol.

168

View full text Add to dashboard Cite

show abstract

“…5). are potent oncogenes in numerous human cancers (17)(18)(19)(20). Even though perturbation of RAS signaling is one of the most common events in carcinogenesis (8), many questions remain open.…”

Section: Nras Isoform 5 Is An Aggressive Variantmentioning

confidence: 99%

NRAS isoforms differentially affect downstream pathways, cell growth, and cell transformation

Eisfeld

Schwind

Hoag

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Significance The members of the rat sarcoma (RAS) gene family Kirsten rat sarcoma viral oncogene homolog, Harvey rat sarcoma viral oncogene homolog, and neuroblastoma RAS viral oncogene homolog (NRAS) belong to the most extensively studied oncogenes and are central players in carcinogenesis. Since their discovery approximately 30 y ago, efforts to target their aberrant activation have not led to major breakthroughs. We herein report the discovery of four so far undescribed variants of NRAS that differ in their expression patterns and, strikingly, in their downstream effects. Our results suggest that NRAS should be studied in the context of its variants. In addition, this discovery may open opportunities to develop more efficient anticancer therapies.

show abstract

“…These viruses induce sarcomas and transform fibroblasts in tissue culture (1,19,25) as well as alter the growth and differentiation of epithelial cells (55) and certain hematopoietic cells (17,34). One well-characterized hematopoietic target of ras oncogenes is a subset of cells within the early lymphoid differentiation pathway which are induced to undergo unrestricted self-renewal and neoplastic conversion in vitro and in vivo in response to these viruses (34).…”

mentioning

confidence: 99%

Myeloid cell transformation by ras-containing murine sarcoma viruses.

Pierce¹,

Aaronson²

1985

Mol. Cell. Biol.

View full text Add to dashboard Cite

BALB and Harvey murine sarcoma viruses contain ras transforming genes capable of altering the proliferation and differentiation of cells within the erythroid and lymphoid lineages (W. D. Hankins and E. M. Scolnick, Cell 26:91-97, 1981; J. H. Pierce and S. A. Aaronson, J. Exp. Med. 156:873-887, 1982; E. M. Scolnick et al., Mol. Cell. Biol. 1:68-74). The present studies demonstrate hematopoietic targets of ras-containing viruses within the myeloid lineage. Diffuse colonies were induced by BALB or Harvey marine sarcoma virus infection of murine bone marrow cells. Generally, these colonies were made up of relatively mature macrophages which exhibited increased self-renewal capacity but eventually underwent terminal differentiation in culture. Cells from one BALB murine sarcoma virus-induced colony displayed phenotypic markers of more immature myelomonocytic cells. This colony, designated BAMC1, readily established as a continuous cell line and was highly malignant in vivo. Exposure of these cells to 12-O-tetradecanoylphorbol-13-acetate led to the induction of a more mature myeloid phenotype, which was associated with decreased growth potential in vitro and in vivo. The effects of the inducing agent were not mediated by an alteration in the level of expression of the ras-coded p21 transforming protein. Our present findings extend the spectrum of targets whose growth is altered by ras-containing retroviruses to cells at several stages of differentiation within each of the major hematopoietic lineages.

show abstract

Multiplicity of Cell Response to a Murine Erythroblastosis Virus1

Cited by 37 publications

References 0 publications

Transcription of c-onc genes c-rasKi and c-fms during mouse development.

Transcription of c-onc genes c-rasKi and c-fms during mouse development.

NRAS isoforms differentially affect downstream pathways, cell growth, and cell transformation

Myeloid cell transformation by ras-containing murine sarcoma viruses.

Contact Info

Product

Resources

About