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Selective immortalization of murine macrophages from fresh bone marrow by a raf/myc recombinant murine retrovirus
Abstract:
Myeloid precursors can be grown in vitro in the presence of specific growth factors; however, their expansion is limited by a competing process of terminal differentiation. Proto-oncogenes seem to be involved in cellular proliferation and/or differentiation and may also play a role in the myelopoietic process. Murine myeloid precursors which are grown in vitro with growth factors respond with augmented self-renewal upon infection with recombinant retroviruses carrying the v-myc or v-src oncogenes, suggesting a synergism or complementation between some viral oncogenes (v-onc) and certain growth factors. We now show that the combination of two v-onc genes (raf and myc) induces the selective proliferation of monocytic cells from fresh murine bone marrow (BM) in the absence of a specific growth factor supplement. Depending on the culture conditions these cells can either differentiate and cease to proliferate or grow continuously, thus mimicking the alternative pathways that can be followed by committed BM stem cells in vivo.
Insights
Viral oncogenes like raf and myc can selectively expand monocytic cells from bone marrow. This discovery offers new insights into controlling myeloid cell proliferation and differentiation for potential therapeutic applications.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Myeloid precursor expansion in vitro is limited by terminal differentiation.
- Proto-oncogenes are implicated in cellular proliferation and differentiation.
- Viral oncogenes (v-onc) can synergize with growth factors to enhance myeloid precursor self-renewal.
Purpose of the Study:
- To investigate the role of combined viral oncogenes in myeloid cell proliferation.
- To determine if specific v-onc combinations can induce selective monocytic cell expansion without growth factors.
Main Methods:
- Infection of murine bone marrow (BM) precursors with recombinant retroviruses carrying raf and myc v-onc genes.
- Culture of infected BM cells under varying conditions to observe proliferation and differentiation.
- Analysis of monocytic cell populations and their growth patterns.
Main Results:
- The combination of raf and myc v-onc genes selectively induced proliferation of monocytic cells from fresh murine BM.
- This proliferation occurred in the absence of specific growth factor supplementation.
- Monocytic cells exhibited alternative fates: terminal differentiation or continuous proliferation based on culture conditions.
Conclusions:
- Co-expression of raf and myc oncogenes can drive selective monocytic cell proliferation.
- These oncogenes can bypass the need for exogenous growth factors in this process.
- The observed in vitro behavior mimics in vivo pathways of committed bone marrow stem cells, suggesting potential for controlled expansion.