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Published on: September 9, 2011
Interferon gamma abrogates the differentiation block in v-myc-expressing U-937 monoblasts
F Oberg1, L G Larsson, R Anton
1Department of Pathology, Uppsala University, University Hospital, Sweden.
Summary
The myc protooncogene inhibits hematopoietic cell differentiation. However, interferon gamma can overcome this block, restoring differentiation without changing myc expression levels, challenging existing theories.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncogenesis
Background:
- The myc protooncogene family plays a crucial role in regulating cell proliferation and differentiation.
- Deregulated myc gene expression is known to inhibit induced differentiation in various cell types, including erythroleukemia and monoblastic cells.
Purpose of the Study:
- To investigate the mechanism by which v-myc inhibits differentiation in U-937 cells induced by phorbol 12-myristate 13-acetate.
- To determine if v-myc also blocks differentiation induced by other agents acting via distinct signaling pathways.
- To explore strategies for overcoming the v-myc-induced differentiation block.
Main Methods:
- Utilized U-937 cells expressing a v-myc gene.
- Induced differentiation using phorbol 12-myristate 13-acetate, 1 alpha, 25-dihydroxycholecalciferol, and retinoic acid.
- Investigated the effect of interferon gamma as a costimulatory factor on differentiation.
- Assessed differentiation by observing macrophage phenotype acquisition and cell cycle arrest.
- Monitored v-myc protein expression and nuclear localization.
Main Results:
- v-myc expression inhibited differentiation induced by phorbol 12-myristate 13-acetate, 1 alpha, 25-dihydroxycholecalciferol, and retinoic acid.
- Interferon gamma, when used as a costimulatory factor, successfully overcame the v-myc-associated differentiation block.
- Costimulation with interferon gamma restored terminal differentiation, characterized by macrophage phenotype and G0/G1 growth arrest, without affecting v-myc levels.
- Interferon gamma alone induced only limited differentiation.
Conclusions:
- Down-regulation of myc is not a universal requirement for terminal differentiation of hematopoietic cells.
- Interferon gamma can induce signaling pathways that circumvent the inhibitory effects of v-myc on differentiation.
- These findings challenge the established view on the role of myc in terminal differentiation.
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