The twist gene is a common target of retroviral integration and transcriptional deregulation in experimental nephroblastoma

被引:23
作者
Pajer, P [1 ]
Pecenka, V [1 ]
Karafiát, V [1 ]
Králová, J [1 ]
Horejsí, Z [1 ]
Dvorák, M [1 ]
机构
[1] Acad Sci Czech Republ, Inst Mol Genet, CR-16637 Prague 6, Czech Republic
关键词
Twist gene; MAV retrovirus; common viral integration site; nephroblastoma;
D O I
10.1038/sj.onc.1206105
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:665 / 673
页数:9
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