Inhibition of the Notch-Hey1 axis blocks embryonal rhabdomyosarcoma tumorigenesis.

ABSTRACT:

Purpose

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood and remains refractory to combined-modality therapy in patients with high risk disease. In skeletal myogenesis, Notch signaling prevents muscle differentiation and promotes proliferation of satellite cell progeny. Given its physiologic role in myogenesis and oncogenic role in other human cancers, we hypothesized that aberrant Notch signaling may contribute to RMS tumorigenesis and present novel therapeutic opportunities.

Experimental design

Human RMS cell lines and tumors were evaluated by immunoblot, IHC, and RT-PCR to measure Notch ligand, receptor, and target gene expression. Manipulation of Notch signaling was accomplished using genetic and pharmacologic approaches. In vitro cell growth, p

SUBMITTER: Belyea BC 

PROVIDER: S-EPMC3241994 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature