Identification of RECK as an evolutionarily conserved tumor suppressor gene for zebrafish malignant peripheral nerve sheath tumors
| Autor: | Suresh K. Mittal, Rashmi Kumari, Yava L. Jones-Hall, Martin R. Silic, Alexandra Nin-Velez, Jer Yen Yang, GuangJun Zhang |
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| Rok vydání: | 2018 |
| Předmět: |
0303 health sciences
Tumor suppressor gene Oncogenomics Gene mutation Biology medicine.disease_cause biology.organism_classification 3. Good health 03 medical and health sciences 0302 clinical medicine Oncology CDKN2A 030220 oncology & carcinogenesis Genetic model medicine Cancer research Carcinogenesis Gene Zebrafish 030304 developmental biology |
| Zdroj: | Oncotarget. 9:23494-23504 |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.25236 |
| Popis: | Malignant peripheral nerve sheath tumors (MPNSTs) are a type of sarcoma with poor prognosis due to their complex genetic changes, invasive growth, and insensitivity to chemo- and radiotherapies. One of the most frequently lost chromosome arms in human MPNSTs is chromosome 9p. However, the cancer driver genes located on it remain largely unknown, except the tumor suppressor gene, p16 (INK4)/CDKN2A. Previously, we identified RECK as a tumor suppressor gene candidate on chromosome 9p using zebrafish-human comparative oncogenomics. In this study, we investigated the tumorigenesis of the reck gene using zebrafish genetic models in both tp53 and ribosomal protein gene mutation background. We also examined the biological effects of RECK gene restoration in human MPNST cell lines. These results provide the first genetic evidence that reck is a bona fide tumor suppressor gene for MPNSTs in zebrafish. In addition, restoration of the RECK gene in human MPNST cells leads to growth inhibition suggesting that the reactivation of RECK could serve as a potential therapeutic strategy for MPNSTs. |
| Databáze: | OpenAIRE |
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