Klin Padiatr 2020; 232(03): e5
DOI: 10.1055/s-0040-1709777
Abstracts

Investigating the role of activated telomerase in genetically engineered neuroblastoma mouse models

LH Werr
1   Children’s Hospital, Dept. of Experimental Pediatric Oncology, University of Cologne
,
J Ackermann
1   Children’s Hospital, Dept. of Experimental Pediatric Oncology, University of Cologne
,
Y Kahlert
1   Children’s Hospital, Dept. of Experimental Pediatric Oncology, University of Cologne
,
J Fischer
1   Children’s Hospital, Dept. of Experimental Pediatric Oncology, University of Cologne
,
FT Wunderlich
2   Center for Molecular Medicine Cologne (CMMC), University of Cologne, Germany
3   Max Planck Institute for Metabolism Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), Cologne, Germany
,
M Fischer
1   Children’s Hospital, Dept. of Experimental Pediatric Oncology, University of Cologne
2   Center for Molecular Medicine Cologne (CMMC), University of Cologne, Germany
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    High-risk neuroblastoma is defined by the presence of telomere maintenance mechanisms, whereas such mechanisms are lacking in spontaneously regressing tumors. To evaluate whether telomerase inactivation impairs initiation and growth of neuroblastoma in in vivo models, we crossbred Th-MYCN;Th-ALKF1174L mice with Tert-/- knockout mice. Preliminary data suggest that the incidence of neuroblastomas is comparable in Th-MYCN;Th-ALKF1174L;Tert+/+ and Th-MYCN;Th-ALKF1174L;Tert-/- mice, but that telomerase-deficient mice show substantially prolonged survival compared to telomerase-proficient mice. In a complementary approach, we are determining the relevance of telomerase activation in neuroblastoma tumorigenesis using a conditional ROSA26-Tert-transgenic mouse model, in which Tert is overexpressed in neuroectodermal cells after Cre-loxP-mediated recombination. In addition to examining the role of telomerase in neuroblastoma pathogenesis, we will use these mouse models to evaluate the growth-inhibitory activity of telomerase inhibitors, such as 6-thio-2ʹ-deoxyguanosine and imetelstat, both of which have shown promising cytotoxic effects in human neuroblastoma cell lines in vitro and in vivo


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    Publication History

    Article published online:
    13 May 2020

    © Georg Thieme Verlag KG
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