Identification of C/EBP? target genes in ALK+ anaplastic large cell lymphoma (ALCL) by gene expression profiling and chromatin immunoprecipitation.

ABSTRACT: C/EBP? (CCAAT enhancer binding protein) is a transcription factor that plays a crucial role in survival and transformation of ALK+ anaplastic large cell lymphoma (ALCL). The aim of this study was to identify the downstream targets of C/EBP? responsible for ALK-mediated oncogenesis. C/EBP? was knocked down in ALK+ ALCL cell lines with a C/EBP?-shRNA, followed by gene expression profiling (GEP). GEP analysis revealed a reproducible signature of genes that were significantly regulated by C/EBP?. Classification into biological categories revealed overrepresentation of genes involved in the immune response, apoptosis and cell proliferation. Transcriptional regulation by C/EBP? was found in 6 of 11 (BCL2A1, G0S2, TRIB1, S100A9, DDX21 and DDIT4) genes investigated by chromatin immunoprecipitation. We demonstrated that BCL2A1, G0S2 and DDX21 play a crucial role in survival and proliferation of ALK+ ALCL cells. DDX21, a gene involved in rRNA biogenesis, was found differentially overexpressed in primary ALK+ ALCL cases. All three candidate genes were validated in primary ALCL cases by either immunohistochemistry or RT-qPCR. In conclusion, we identified and validated several key C/EBP?-regulated genes with major impact on survival and cell growth in ALK+ ALCL, supporting the central role of C/EBP? in ALK-mediated oncogenesis.

SUBMITTER: Bonzheim I 

PROVIDER: S-EPMC3669320 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature