Experimental glioma with high bHLH expression harbor increased replicative stress and are sensitive toward ATR inhibition.

ABSTRACT:

Background

The overexpression of (basic)helix-loop-helix ((b)HLH) transcription factors (TFs) is frequent in malignant glioma. We investigated molecular effects upon disruption of the (b)HLH network by a dominant-negative variant of the E47 protein (dnE47). Our goal was to identify novel molecular subgroup-specific therapeutic strategies.

Methods

Glioma cell lines LN229, LNZ308, and GS-2/GS-9 were lentivirally transduced. Functional characterization included immunocytochemistry, immunoblots, cytotoxic, and clonogenic survival assays in vitro, and latency until neurological symptoms in vivo. Results of cap analysis gene expression and RNA-sequencing were further validated by immunoblot, flow cytometry, and functional assays in vitro.

Results

The induction of dnE47-RFP

SUBMITTER: Koch MS 

PROVIDER: S-EPMC7592426 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature