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Canonical Notch signaling is not required for the growth of Hedgehog pathway-induced medulloblastoma

Oncogene volume 29, pages 3465–3476 (2010)Cite this article

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Abstract

Current treatment for medulloblastoma is successful in more than half of all cases but results in substantial disability in survivors. Accordingly, there is considerable interest in drugs that may target specific signaling pathways activated in the tumors, with inhibitors of both the Hedgehog and Notch pathways currently proposed as possible therapeutics. Here, we tested the hypothesis that Notch pathway inhibition in vivo may block the formation of Hedgehog-dependent medulloblastoma. We took the general approach of using a cre recombinase under the control of the GFAP promoter to generate medulloblastoma in mice carrying a conditional Ptc1 allele and introduced a conditional RBP-J allele to ablate canonical Notch signaling. Loss of RBP-J from the developing cerebellum led to a modest loss of stem cells and an overall developmental delay. These phenotypes could be partially compensated by activation of the Hedgehog pathway. Hedgehog-dependent medulloblastoma were not blocked by loss of RBP-J, indicating that canonical Notch signaling is not required for tumor initiation and growth in this model.

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Acknowledgements

E Julian is an ANZ Trustees Research Scholar. This work was supported by funds from the National Health and Medical Research Council of Australia, The John Trivett Foundation, the ARC Special Research Centre for Functional and Applied Genomics and the Australian Cancer Research Fund. We thank Professor Tasuku Honjo for RBP-J mice and Professor Ryoichiro Kageyama and Dr Zeng-jie Yang for helpful discussions.

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  1. Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia

    E Julian, R K Dave, J P Robson & B J Wainwright

  2. Department of Paediatrics and Child Health, University of Queensland, Brisbane, Australia

    A R Hallahan

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Julian, E., Dave, R., Robson, J. et al. Canonical Notch signaling is not required for the growth of Hedgehog pathway-induced medulloblastoma. Oncogene 29, 3465–3476 (2010). https://doi.org/10.1038/onc.2010.101

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