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

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 0 UTR region, right upstream from the ATG initiation codon. The integrated proviruses were deleted at their 5 0 ends. As a consequence, twist transcription became controlled by the retroviral 3 0 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.

Identification of a novel function of TWIST, a bHLH protein, in the development of acquired taxol resistance in human cancer cells

“…In the present study, we found TWIST expression in cell lines derived from four types of carcinomas originated from nasopharynx, bladder, ovary and prostate (Figure 5), supporting the hypothesis that in addition to osteogenesis, TWIST may also play a role in tumorigenesis. This is further supported by a recent study that activation of TWIST may contribute to tumorigenes, because it was identified as a common target for retro viral integration in MAV2 virus-induced chicken nephroblastoma (Pajer et al, 2003). The results presented in this study have shown that TWIST is not only commonly expressed in human carcinomas, but may also play an important role in inducing acquired resistance to microtubule-disrupting anticancer drugs.…”

Frequent genomic abnormalities at TWIST in human pediatric osteosarcomas

“…At diagnosis, 15 patients already had a metastatic disease (patients 7,12,13,16,24,28,37,41,45,49,53,56,57,58, and 61). Independently from this diagnostic factor, patients were classified as good responders (GRs) (38 cases) and poor responders (PRs) (35 cases) to preoperative chemotherapy, according to the surgical histopathologic grading reported by Huvos et al 22 Only one patient was not assessable.…”

“…[9][10][11] In contrast, abnormal activation of TWIST has been implicated in several human cancers, as in gastric cancer 12 and nephroblastoma. 13 In addition, TWIST was shown to play a role in the formation of rhabdomyosarcoma by inhibiting apoptotis 14 and also by halting terminal differentiation of muscle cells 14 and mammary gland. 15 Furthermore, recent reports related that the activation of TWIST is linked to the epithelial-to-mesenchymal switch and promotes tumor cell metastasis from soft tissues.…”

Msx2andTwistcooperatively control the development of the neural crest-derived skeletogenic mesenchyme of the murine skull vault

“…Transplantation experiments demonstrated that Twist is required both in neural crest cells and in paraxial mesoderm for the guidance of migrating neural crest cells. In addition, Twist is required for neural crest differentiation, whereas in wild-type embryos, Sox10 expression is downregulated progressively in migratory neural crest cells, in mutant embryos it is maintained at a high level, suggesting that neural crest cells may be arrested at an early stage of differentiation (Soo et al, 2002 (Maestro et al, 1999;Gullaud et al, 2003;Pajer et al, 2003).…”