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Expression data of cHL cell lines after FOXO1 activation

ABSTRACT: FOXO1 is highly expressed in normal B cells and in most types of non-Hodgkinl lymphoma. In Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma(cHL) expression of FOXO1 is low or absent. We overexpressed constitutively active mutant of FOXO1 fused in frame with estrogen receptor ligand-binding domain (FOXO1(3A)ER), which can be activated by 4-Hydroxytamoxifen (4-OHT), in cHL cell lines KM-H2 and L428. Activation of the FOXO1 with 4-OHT resulted in inhibition of proliferation and apoptosis. Using gene-expression array we found that FOXO1 activates transcription of known and potential tumor suppressor genes: CDKN1B, PMAIP1, BCL2L11, TNFSF10, FBXO32, CBLB). Of note, FOXO1 repressed transcription of several cytokines and cytokine receptors, which are known tobe involved in pathogenesis of cHL (e.g. CCL5, CXCR5, TNFRSF8). Taken togather our data indicate important role of FOXO1 repression in pathogenesis of cHL.

ORGANISM(S): Homo sapiens

PROVIDER: GSE29545 | GEO | 2012/06/01

SECONDARY ACCESSION(S): PRJNA141427

REPOSITORIES: GEO

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Project description:Background Epigenetic changes are involved in the extinction of the B-cell gene expression program of classical Hodgkin lymphoma. However, little is known regarding epigenetic similarities between classical Hodgkin lymphoma and plasma cell myeloma cells, both of which share an extinction of the gene expression program of mature B-cells. Design and methods Global histone H3 acetylation patterns were determined in cell lines derived from classical Hodgkin lymphoma, plasma cell myeloma and B-cell lymphoma by chromatin immunoprecipitation and subsequent hybridization onto promoter tiling arrays. H3K27 trimethylation was analyzed by chromatin immunoprecipitation and real-time DNA-PCR for selected genes. Epigenetic modifications were compared to gene expression data. Results B-cell characteristic genes were hypoacetylated in classical Hodgkin lymphoma and plasma cell myeloma cell lines, as demonstrated by comparison of their histone H3 acetylation patterns to those of B-cell lines. However, the number of genes jointly hyperacetylated and expressed in classical Hodgkin lymphoma and plasma cell myeloma cell lines, such as IFR4/MUM1 and RYBP, is limited. Moreover, H3K27 trimethylation for selected B-cell characteristic genes revealed that this additional epigenetic silencing is much more prevalent in classical Hodgkin lymphoma as compared to plasma cell myeloma. Conclusion Our epigenetic data support the view that classical Hodgkin lymphoma is characterized by an abortive plasma cell differentiation with a down-regulation of B-cell characteristic genes but without activation of most plasma cell typical genes. Gene expression analysis of Hodgkin lymphoma (cHL) and B-cell lines: Microarray data for three Hodgkin lymphoma cell lines (KM-H2, L1236, L428) and the B-cell line Namalwa that were published previously by our group (GEO accession GSE8388) were analyzed together with newly generated data for the B-cell lines SU-DHL4 and SU-DHL6. For all cell lines, RNA was isolated according to standard protocols (Qiagen, Hilden, Germany) and used for Affymetrix GeneChip hybridization (HG-U133A). Microarrays were normalized using RMA, and differential expression was calculated using moderated t-test. The gene expression profiles of the cell lines were generated in duplicates.

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Expression data of cHL cell lines after FOXO1 activation

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