Myeloblastosis-associated virus 2 (MAV-2) is a highly tumorigenic simple avian retrovirus. Chickens infected in ovo with MAV-2 develop tumors in the kidneys, lungs, and liver with a short latency, less than 8 weeks. Here we report the results of molecular analyses of MAV-2-induced liver tumors that fall into three classes: hepatic hemangiosarcomas (HHSs), intrahepatic cholangiocarcinomas (ICCs), and hepatocellular carcinomas (HCCs). Comprehensive inverse PCR-based screening of 92 chicken liver tumors revealed that in ca. 86% of these tumors, MAV-2 provirus had integrated into one of four gene loci: HRAS, EGFR, MET, and RON Insertionally mutated genes correlated with tumor type: HRAS was hit in HHSs, MET in ICCs, RON mostly in ICCs, and EGFR mostly in HCCs. The provirus insertions led to the overexpression of the affected genes and, in the case of EGFR and RON, also to the truncation of exons encoding the extracellular ligand-binding domains of these transmembrane receptors. The structures of truncated EGFR and RON closely mimic the structures of oncogenic variants of these genes frequently found in human tumors (EGFRvIII and sfRON).IMPORTANCE These data describe the mechanisms of oncogenesis induced in chickens by the MAV-2 retrovirus. They also show that molecular processes converting cellular regulatory genes to cancer genes may be remarkably similar in chickens and humans. We suggest that the MAV-2 retrovirus-based model can complement experiments performed using mouse models and provide data that could translate to human medicine.
- MeSH
- cholangiokarcinom genetika virologie MeSH
- geny erbB-1 * MeSH
- hemangiosarkom genetika virologie MeSH
- hepatocelulární karcinom genetika virologie MeSH
- integrace viru MeSH
- inzerční mutageneze * MeSH
- karcinogeneze * MeSH
- kur domácí genetika MeSH
- lidé MeSH
- nádory jater genetika virologie MeSH
- onkogeny MeSH
- protoonkogenní proteiny c-met genetika MeSH
- proviry genetika fyziologie MeSH
- ptačí proteiny genetika MeSH
- tyrosinkinasové receptory genetika MeSH
- virus ptačí myeloblastózy genetika fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
v-myb oncogene of avian myeloblastosis virus (AMV) transforms myelomonocytic cells in vitro and induces acute monoblastic leukemia in vivo. The transforming effect of the v-myb can be suppressed using phorbol ester (TPA) or histone deacetylase inhibitor trichostatin A (TSA), the inducers of cell differentiation that are in clinical trials. In this study, we used proteomics-based approach to identify proteins with variable expression in differentiated BM2 cells. Proteome variations induced by TPA and TSA were compared to examine the mechanism of differentiation-promoting effects of these drugs. We found that expression of several proteins participating in cell cytoskeleton rearrangement, heat shock response, proteosynthesis and cell signaling was altered in TPA- or TSA-treated cells. We present here the first comparative proteome analysis of v-myb-transformed monoblasts BM2 focused on identification of proteins involved in their terminal differentiation.
- MeSH
- 2D gelová elektroforéza metody MeSH
- buněčná diferenciace fyziologie účinky léků MeSH
- financování organizované MeSH
- forbolové estery farmakologie MeSH
- hmotnostní spektrometrie metody MeSH
- kur domácí MeSH
- kyseliny hydroxamové farmakologie MeSH
- monocyty fyziologie účinky léků MeSH
- onkogenní proteiny v-myb fyziologie účinky léků MeSH
- proteiny analýza fyziologie MeSH
- proteomika metody MeSH
- transformované buněčné linie MeSH
- virus ptačí myeloblastózy fyziologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- MeSH
- DNA vazebné proteiny genetika MeSH
- financování organizované MeSH
- geny ras genetika MeSH
- integrace viru genetika MeSH
- koncové repetice MeSH
- kuřecí embryo MeSH
- lidé MeSH
- mapování chromozomů MeSH
- nádory ledvin genetika virologie MeSH
- nemoci drůbeže genetika MeSH
- onkogenní proteiny genetika MeSH
- onkogeny genetika MeSH
- polymerázová řetězová reakce MeSH
- proviry genetika MeSH
- ptačí proteiny genetika MeSH
- transkripční faktor Twist MeSH
- tumor supresorové geny MeSH
- virus ptačí myeloblastózy genetika MeSH
- Wilmsův nádor genetika virologie MeSH
- zvířata MeSH
- Check Tag
- kuřecí embryo MeSH
- lidé MeSH
- zvířata MeSH
