liu.seSearch for publications in DiVA
Change search
ReferencesLink to record
Permanent link

Direct link
Inhibitors of mammalian target of rapamycin downregulate MYCN protein expression and inhibit neuroblastoma growth in vitro and in vivo
Show others and affiliations
2008 (English)In: Oncogene, ISSN 0950-9232, Vol. 27, no 20, 2910-2922 p.Article in journal (Refereed) Published
Abstract [en]

Mammalian target of rapamycin (mTOR) has been shown to play an important function in cell proliferation, metabolism and tumorigenesis, and proteins that regulate signaling through mTOR are frequently altered in human cancers. In this study we investigated the phosphorylation status of key proteins in the PI3K/AKT/mTOR pathway and the effects of the mTOR inhibitors rapamycin and CCI-779 on neuroblastoma tumorigenesis. Significant expression of activated AKT and mTOR were detected in all primary neuroblastoma tissue samples investigated, but not in non-malignant adrenal medullas. mTOR inhibitors showed antiproliferative effects on neuroblastoma cells in vitro. Neuroblastoma cell lines expressing high levels of MYCN were significantly more sensitive to mTOR inhibitors compared to cell lines expressing low MYCN levels. Established neuroblastoma tumors treated with mTOR inhibitors in vivo showed increased apoptosis, decreased proliferation and inhibition of angiogenesis. Importantly, mTOR inhibitors induced downregulation of vascular endothelial growth factor A (VEGF-A) secretion, cyclin D1 and MYCN protein expression in vitro and in vivo. Our data suggest that mTOR inhibitors have therapeutic efficacy on aggressive MYCN amplified neuroblastomas. © 2008 Nature Publishing Group All rights reserved.

Place, publisher, year, edition, pages
2008. Vol. 27, no 20, 2910-2922 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-44865DOI: 10.1038/sj.onc.1210938Local ID: 78014OAI: diva2:265727
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2011-01-10

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Kågedal, Bertil
By organisation
Faculty of Health SciencesClinical ChemistryDepartment of Clinical Chemistry
In the same journal
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 12 hits
ReferencesLink to record
Permanent link

Direct link