Chicken Models of Retroviral Insertional Mutagenesis

Pečenka, Vladimír; Pajer, Petr; Karafiát, Vı́t; Dvořák, Michal

doi:10.1007/978-1-4419-7656-7_4

Cited by 2 publications

(2 citation statements)

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“…Considering provirus positions and orientations, all insertions into CISs corresponded to the promoter insertion mechanism where the transcription of a resident cellular gene is driven by the inserted proviral promoter (30). No case of enhancer insertion (where provirus regulatory sequences boost, at a distance, the gene's transcription from its own promoter) or the formation of a recombinant oncogenetransducing retrovirus was observed.…”

Section: Discussionmentioning

confidence: 99%

“…The structure of MAV-2 provirus plus sites of start (bent arrow), splicing (dotted lines), and termination [poly(A)] of its transcript are shown (upper drawing). The activity of the 3= LTR promoter in a nondefective provirus is blocked by transcriptional interference(30). The mechanism of formation of hybrid MAV-2/cancer gene mRNAs is suggested (lower drawings).…”

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confidence: 99%

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HRAS , EGFR , MET , and RON Genes Are Recurrently Activated by Provirus Insertion in Liver Tumors Induced by the Retrovirus Myeloblastosis-Associated Virus 2

Pečenka

Pajer

Karafiát

et al. 2017

J Virol

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Myeloblastosis-associated virus 2 (MAV-2) is a highly tumorigenic simple avian retrovirus. Chickens infected 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:, ,, and Insertionally mutated genes correlated with tumor type: was hit in HHSs, in ICCs, mostly in ICCs, and mostly in HCCs. The provirus insertions led to the overexpression of the affected genes and, in the case of and , also to the truncation of exons encoding the extracellular ligand-binding domains of these transmembrane receptors. The structures of truncated and closely mimic the structures of oncogenic variants of these genes frequently found in human tumors ( and ). 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.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

HRAS , EGFR , MET , and RON Genes Are Recurrently Activated by Provirus Insertion in Liver Tumors Induced by the Retrovirus Myeloblastosis-Associated Virus 2

Pečenka

Pajer

Karafiát

et al. 2017

J Virol

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Egg Yolk Phospholipids Enriched with 1-O-Octadecyl-2-Oleoyl-sn-Glycero-3-Phospho-(N-Palmitoyl) Ethanolamine Inhibit Development of Experimentally Induced Tumours

Karafiát,

Veselý,

Dvořák

2014

Fol. Biol.

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Dietary phospholipids (PLs) and their derivatives have proved active in suppression of various health problems and conditions including cancer. In this work we compared the effect of dietary phospholipids from hen egg yolk enriched with N-acyl ether-phosphatidyl ethanolamine (NAEPE) termed bioactive phospholipids (BAP+ preparation) with PLs lacking NAEPE (BAP– preparation) on the growth of transformed cells in vitro and on the promotion and progression of experimental tumours in vivo. For the in vivo experiments we used the chicken model in which liver, lung, and kidney tumours arose via natural selection from single cells initiated by experimentally introduced somatic mutations caused by insertional mutagenesis. Mutagenized animals were fed BAP+ or BAP– diet in various regimens. We observed that BAP+ at low concentrations killed cells of various tumour cell lines in culture but did not compromise viability of non-transformed cells. Oral administration of the BAP+ preparation efficiently reduced progression of all tumour types. However, it did not significantly reduce the number of already initiated tumours and their growth when BAP+ was discontinued. Our data suggest that NAEPE combined with hen egg PLs significantly interferes with tumour progression, possibly through the inhibition of tumour cell viability.

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Chicken Models of Retroviral Insertional Mutagenesis

Cited by 2 publications

References 154 publications

HRAS , EGFR , MET , and RON Genes Are Recurrently Activated by Provirus Insertion in Liver Tumors Induced by the Retrovirus Myeloblastosis-Associated Virus 2

HRAS , EGFR , MET , and RON Genes Are Recurrently Activated by Provirus Insertion in Liver Tumors Induced by the Retrovirus Myeloblastosis-Associated Virus 2

Egg Yolk Phospholipids Enriched with 1-O-Octadecyl-2-Oleoyl-sn-Glycero-3-Phospho-(N-Palmitoyl) Ethanolamine Inhibit Development of Experimentally Induced Tumours

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