Curtin University Homepage
  • Library
  • Help
    • Admin

    espace - Curtin’s institutional repository

    JavaScript is disabled for your browser. Some features of this site may not work without it.
    View Item 
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item

    A GFP-Tagged Gross Deletion on Chromosome 1 Causes Malignant Peripheral Nerve Sheath Tumors and Carcinomas in Zebrafish

    237857_237857.pdf (5.467Mb)
    Access Status
    Open access
    Authors
    Astone, M.
    Pizzi, M.
    Peron, M.
    Domenichini, Alice
    Guzzardo, V.
    Töchterle, S.
    Tiso, N.
    Rugge, M.
    Meyer, D.
    Argenton, F.
    Vettori, A.
    Date
    2015
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    Astone, M. and Pizzi, M. and Peron, M. and Domenichini, A. and Guzzardo, V. and Töchterle, S. and Tiso, N. et al. 2015. A GFP-Tagged Gross Deletion on Chromosome 1 Causes Malignant Peripheral Nerve Sheath Tumors and Carcinomas in Zebrafish. PLoS One. 10 (12): pp. e0145178.
    Source Title
    PLoS One
    DOI
    10.1371/journal.pone.0145178
    School
    School of Biomedical Sciences
    Remarks

    This open access article is distributed under the Creative Commons license http://creativecommons.org/licenses/by/4.0/

    URI
    http://hdl.handle.net/20.500.11937/10877
    Collection
    • Curtin Research Publications
    Abstract

    Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive soft-tissue sarcomas, characterized by complex karyotypes. The molecular bases of such malignancy are poorly understood and efficient targeted molecular therapies are currently lacking. Here we describe a novel zebrafish model of MPNSTs, represented by the transgenic mutant line Tg(-8.5nkx2.2a:GFP)ia2. ia2 homozygous animals displayed embryonic lethality by 72 hpf, while the heterozygotes develop visible tumor masses with high frequency in adulthood. Histological and immunohistochemical examination revealed aggressive tumors with either mesenchymal or epithelial features. The former (54% of the cases) arose either in the abdominal cavity, or as intrathecal/intraspinal lesions and is composed of cytokeratin-negative spindle cells with fascicular/storiform growth pattern consistent with zebrafish MPNSTs. The second histotype was composed by polygonal or elongated cells, immunohistochemically positive for the pan-cytokeratin AE1/AE3. The overall histologic and immunohistochemical features were consistent with a malignant epithelial neoplasm of possible gastrointestinal/pancreatic origin. With an integrated approach, based on microsatellite (VNTR) and STS markers, we showed that ia2 insertion, in Tg(-8.5nkx2.2a:GFP)ia2 embryos, is associated with a deletion of 15.2 Mb in the telomeric portion of chromosome 1. Interestingly, among ia2 deleted genes we identified the presence of the 40S ribosomal protein S6 gene that may be one of the possible drivers for the MPNSTs in ia2 mutants.Thanks to the peculiar features of zebrafish as animal model of human cancer (cellular and genomic similarity, transparency and prolificacy) and the GFP tag, the Tg(-8.5nkx2.2a:GFP)ia2 line provides a manageable tool to study in vivo with high frequency MPNST biology and genetics, and to identify, in concert with the existing zebrafish MPNST models, conserved relevant mechanisms in zebrafish and human cancer development.

    Related items

    Showing items related by title, author, creator and subject.

    • Potential Role of Natural Compounds as Anti-Angiogenic Agents in Cancer
      Shanmugam, M.; Warrier, S.; Kumar, A.; Sethi, G.; Arfuso, Frank (2017)
      BACKGROUND: Neovascularization, also known as angiogenesis, is the process of capillary sprouting from pre-existing blood vessels. This physiological process is a hallmark event in normal embryonic development as blood ...
    • Mechanisms underlying acquired platinum resistance in high grade serous ovarian cancer - a mini review
      Binju, M.; Padilla, M.; Singomat, T.; Kaur, Pritinder; Suryo Rahmanto, Y.; Cohen, P.; Yu, Yu (2019)
      © 2018 Elsevier B.V. Background: Advanced epithelial ovarian cancer is one of the hardest human malignancies to treat. Standard treatment involves cytoreductive surgery and platinum-based chemotherapy, however, median ...
    • Apoptosis induction of poly-S-nitrosated human serum albumin in resistant solid tumor under hypoxia can be restored by phosphodiesterase 5 inhibition
      Ikeda, M.; Ishima, Y.; Chuang, Victor; Ikeda, T.; Kinoshita, R.; Watanabe, H.; Ishida, T.; Otagiri, M.; Maruyama, T. (2016)
      Poly-S-nitrosated human serum albumin (Poly-SNO-HSA) delivered and accumulated nitric oxide (NO) in tumors and induces apoptosis. Tumor hypoxia is strongly associated with malignant progression and tumor resistance to ...
    Advanced search

    Browse

    Communities & CollectionsIssue DateAuthorTitleSubjectDocument TypeThis CollectionIssue DateAuthorTitleSubjectDocument Type

    My Account

    Admin

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Follow Curtin

    • 
    • 
    • 
    • 
    • 

    CRICOS Provider Code: 00301JABN: 99 143 842 569TEQSA: PRV12158

    Copyright | Disclaimer | Privacy statement | Accessibility

    Curtin would like to pay respect to the Aboriginal and Torres Strait Islander members of our community by acknowledging the traditional owners of the land on which the Perth campus is located, the Whadjuk people of the Nyungar Nation; and on our Kalgoorlie campus, the Wongutha people of the North-Eastern Goldfields.