Identification of C/EBPβ Target Genes in ALK plus Anaplastic Large Cell Lymphoma (ALCL) by Gene Expression Profiling and Chromatin Immunoprecipitation

被引：33

作者：

Bonzheim, Irina ^{[1
,2
,3
]}

Irmler, Martin ^{[4
]}

Klier-Richter, Margit ^{[1
,2
,3
]}

Steinhilber, Julia ^{[1
,2
]}

Anastasov, Natasa ^{[3
]}

Schaefer, Sabine ^{[1
,2
]}

Adam, Patrick ^{[1
,2
]}

Beckers, Johannes ^{[4
,6
]}

Raffeld, Mark ^{[5
]}

Fend, Falko ^{[1
,2
]}

Quintanilla-Martinez, Leticia ^{[1
,2
,3
]}

机构：

[1] Univ Tubingen Hosp, Inst Pathol & Neuropathol, Tubingen, Germany

[2] Univ Tubingen, Ctr Comprehens Canc, Tubingen, Germany

[3] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen GmbH, Inst Pathol, Neuherberg, Germany

[4] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen GmbH, Inst Expt Genet, Neuherberg, Germany

[5] NCI, Natl Inst Hlth, Bethesda, MD 20892 USA

[6] Tech Univ Munich, Chair Expt Genet, Freising Weihenstephan, Germany

来源：

PLOS ONE | 2013年 / 8卷 / 05期

关键词：

NF-KAPPA-B; BINDING-PROTEIN-BETA; RNA HELICASE-II/GU; SIGNALING PATHWAY; CYCLIN D1; II GU; TRANSCRIPTION; KINASE; SURVIVAL; DOMAINS;

D O I：

10.1371/journal.pone.0064544

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

C/EBP beta (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 beta responsible for ALK-mediated oncogenesis. C/EBP beta was knocked down in ALK+ ALCL cell lines with a C/EBP beta-shRNA, followed by gene expression profiling (GEP). GEP analysis revealed a reproducible signature of genes that were significantly regulated by C/EBP beta. Classification into biological categories revealed overrepresentation of genes involved in the immune response, apoptosis and cell proliferation. Transcriptional regulation by C/EBP beta 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 beta-regulated genes with major impact on survival and cell growth in ALK+ ALCL, supporting the central role of C/EBP beta in ALK-mediated oncogenesis.

引用

页数：15

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