Targeting the EWS/ETS transcriptional program by BET bromodomain inhibition in Ewing sarcoma

ABSTRACT: Ewing sarcomas (ES) are highly malignant, osteolytic bone or soft tissue tumors, which are characterized by early metastasis into lung and bone. Genetically, ES are defined by balanced chromosomal EWS/ETS translocations, which give rise to chimeric proteins (EWS-ETS) that generate an oncogenic transcriptional program associated with altered epigenetic marks throughout the genome. By use of an inhibitor (JQ1) blocking BET bromodomain binding proteins (BRDs) we strikingly observed a strong down-regulation of the predominant EWS-ETS protein EWS/FLI1 in a dose dependent manner. Microarray analysis further revealed JQ1 treatment to block a typical ES associated expression program. The effect on this expression program could be mimicked by RNA interference with BRD3 or BRD4 expression, indicatin

ORGANISM(S): Homo sapiens

SUBMITTER: Guenther Richter 

PROVIDER: E-GEOD-72673 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress