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Notch3 signaling initiates choroid plexus tumor formation

Oncogene volume 25, pages 487–491 (2006)Cite this article

Abstract

Notch3 has been studied in the context of brain development, but whether it plays a role in the formation of brain tumors is unclear. We demonstrate that the introduction of constitutively active Notch3 into periventricular cells of embryonic day 9.5 mice causes the formation of choroid plexus tumors (CPTs). Tumors arose in the fourth ventricles in 83% of animals and were associated with hydrocephalus. They were microscopically highly similar to choroid plexus papillomas in humans, with an ongoing proliferation rate of 4–6%. Signs of Notch pathway activity were also present in human choroid plexus lesions, and receptor mRNA levels in papillomas were elevated over those in non-neoplastic choroid plexus. Notch2 was overexpressed approximately 500-fold in one case, suggesting that the role of this pathway in CPTs may not be specific to Notch3. Our findings indicate that activated Notch3 can function as an oncogene in the developing brain, and link the Notch pathway to human CPT pathogenesis.

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Acknowledgements

We thank Dr Tetsuo Sudo for kindly providing Hes1 antibody. This work was supported by grants from the Children's Cancer Foundation and NINDS K08NS43279 to CGE, by a Kimmel Scholar Award to NG, and by NINDS K08NS041342 to MW. CGE, MW and NG are all recipients of Burroughs Wellcome Fund Career Awards in the Biomedical Sciences.

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Author notes

  1. L Dang and X Fan: These two authors contributed equally to this work

Authors and Affiliations

  1. Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    L Dang & N Gaiano

  2. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    L Dang & N Gaiano

  3. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    X Fan, A Chaudhry & C G Eberhart

  4. Departments of Neurology and Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA

    M Wang

  5. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    N Gaiano

  6. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    N Gaiano & C G Eberhart

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  1. L Dang
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  2. X Fan
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  3. A Chaudhry
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  4. M Wang
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  5. N Gaiano
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  6. C G Eberhart
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Corresponding authors

Correspondence to N Gaiano or C G Eberhart.

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Dang, L., Fan, X., Chaudhry, A. et al. Notch3 signaling initiates choroid plexus tumor formation. Oncogene 25, 487–491 (2006). https://doi.org/10.1038/sj.onc.1209074

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