Format

Send to

Choose Destination
Cancer Res. 2010 Jun 1;70(11):4666-75. doi: 10.1158/0008-5472.CAN-09-3970. Epub 2010 May 18.

Regulation of insulin-like growth factor-mammalian target of rapamycin signaling by microRNA in childhood adrenocortical tumors.

Author information

1
Institut de Pharmacologie Moléculaire et Cellulaire, 660 route des Lucioles, 06560 Valbonne, France.

Abstract

MicroRNAs (miRNAs) act at the posttranscriptional level to control gene expression in virtually every biological process, including oncogenesis. Here, we report the identification of a set of miRNAs that are differentially regulated in childhood adrenocortical tumors (ACT), including miR-99a and miR-100. Functional analysis of these miRNAs in ACT cell lines showed that they coordinately regulate expression of the insulin-like growth factor-mammalian target of rapamycin (mTOR)-raptor signaling pathway through binding sites in their 3'-untranslated regions. In these cells, the active Ser(2448)-phosphorylated form of mTOR is present only in mitotic cells in association with the mitotic spindle and midbody in the G(2)-M phases of the cell cycle. Pharmacologic inhibition of mTOR signaling by everolimus greatly reduces tumor cell growth in vitro and in vivo. Our results reveal a novel mechanism of regulation of mTOR signaling by miRNAs, and they lay the groundwork for clinical evaluation of drugs inhibiting the mTOR pathway for treatment of adrenocortical cancer.

PMID:
20484036
PMCID:
PMC2880211
DOI:
10.1158/0008-5472.CAN-09-3970
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center