Abstract
The genes involved in the transformation of kidney blastema cells were searched for in avian nephroblastomas induced by the MAV2 retrovirus. The twist gene was identified as a common site of provirus integration in tumor cells. Twist was rearranged by the MAV2 provirus in three out of 76 independent nephroblastoma samples. The MAV2 integration sites were localized within 40 nucleotides of the twist 5′UTR region, right upstream from the ATG initiation codon. The integrated proviruses were deleted at their 5′ends. As a consequence, twist transcription became controlled by the retroviral 3′LTR promoter and was strongly upregulated, more than 200 times. In addition, 2–100 times elevated twist transcription was also detected in the majority of other nephroblastoma samples not containing MAV2 in the twist locus. We propose that chicken nephroblastoma originates from a single blastemic cell in which the MAV retrovirus, through its integration, has deregulated specific combinations of genes controlling proliferation and differentiation. The activation of the twist gene expression appears to contribute to tumorigenesis, as there is an in vivo positive selection of tumor cell clones containing the twist gene hyperactivated by MAV2 sequences inserted within the twist promoter.
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Acknowledgements
The authors thank Petr Bartûněk and Daniel Elleder for the critical reading of the manuscript, helpful comments and discussion. The assistance of Šárka Takáčová in manuscript preparation is also greatly acknowledged. This work was supported by grants 301/98/K042 and 204/00/0554 from the Grant Agency of the Czech Republic.
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Pajer, P., Pečenka, V., Karafiát, V. et al. The twist gene is a common target of retroviral integration and transcriptional deregulation in experimental nephroblastoma. Oncogene 22, 665–673 (2003). https://doi.org/10.1038/sj.onc.1206105
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DOI: https://doi.org/10.1038/sj.onc.1206105
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