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Inhibitors of ribosome biogenesis repress the growth of MYCN-amplified neuroblastoma

Permanent lenke
https://hdl.handle.net/10037/18268
DOI
https://doi.org/10.1038/s41388-018-0611-7
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article.pdf (8.955Mb)
Publisert versjon (PDF)
Dato
2018-12-12
Type
Journal article
Tidsskriftartikkel
Peer reviewed

Forfatter
Hald, Øyvind Holsbø; Olsen, Lotte; Gallo-Oller, Gabriel; Elfman, Lotta Helena Maria; Løkke, Cecilie; Kogner, Per; Sveinbjørnsson, Baldur; Flægstad, Trond; Johnsen, John Inge; Einvik, Christer
Sammendrag
Abnormal increases in nucleolar size and number caused by dysregulation of ribosome biogenesis has emerged as a hallmark in the majority of spontaneous cancers. The observed ribosome hyperactivity can be directly induced by the MYC transcription factors controlling the expression of RNA and protein components of the ribosome. Neuroblastoma, a highly malignant childhood tumor of the sympathetic nervous system, is frequently characterized by MYCN gene amplification and high expression of MYCN and c-MYC signature genes. Here, we show a strong correlation between high-risk disease, MYCN expression, poor survival, and ribosome biogenesis in neuroblastoma patients. Treatment of neuroblastoma cells with quarfloxin or CX-5461, two small molecule inhibitors of RNA polymerase I, suppressed MycN expression, induced DNA damage, and activated p53 followed by cell cycle arrest or apoptosis. CX-5461 repressed the growth of established MYCN-amplified neuroblastoma xenograft tumors in nude mice. These findings suggest that inhibition of ribosome biogenesis represent new therapeutic opportunities for children with high-risk neuroblastomas expressing high levels of Myc.
Er en del av
Hald, Ø.H. (2020). Molecular aspects of high-risk neuroblastoma and novel therapeutic opportunities. (Doctoral thesis). https://hdl.handle.net/10037/18271.
 
Olsen, L. (2020). Exploring and targeting novel cancer networks in multidrug resistant neuroblastoma. (Doctoral thesis). https://hdl.handle.net/10037/18495.
Forlag
Springer Nature
Sitering
Hald Ø, Olsen L, Gallo-Oller, Elfman, Løkke C, Kogner P, Sveinbjørnsson B, Flægstad T, Johnsen JI, Einvik C. Inhibitors of ribosome biogenesis repress the growth of MYCN-amplified neuroblastoma.. Oncogene. 2018:1-14
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  • Artikler, rapporter og annet (klinisk medisin) [1974]
Copyright 2018 The Author(s)
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