The Transcription Factor Evi-1 Is Overexpressed, Promotes Proliferation, and Is Prognostically Unfavorable in Infratentorial Ependymomas

Koos, Björn; Bender, Sebastian; Witt, Hendrik; Mertsch, Sonja; Felsberg, Joerg; Beschorner, Rudi; Korshunov, Andrey; Riesmeier, Barbara; Pfister, Stefan M.; Paulus, Werner; Hasselblatt, Martin

doi:10.1158/1078-0432.ccr-11-0175

Cited by 33 publications

(20 citation statements)

References 29 publications

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“…Prdm14 is overexpressed in breast cancer (Nishikawa et al, 2007) and causes lymphoid leukaemia (Dettman et al, 2011). Prdm3 is a susceptibility locus in nasopharyngeal carcinoma (Bei et al, 2010) and a variety of other solid tumours (Koos et al, 2011;Sugita et al, 2000). In addition, Prdm13 is a tumour antigen associated with medulloblastoma (Behrends et al, 2003).…”

Section: Box 2 Prdms In Cancer and Other Diseasesmentioning

confidence: 99%

The Prdm family: expanding roles in stem cells and development

2012

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SummaryMembers of the Prdm family are characterized by an Nterminal PR domain that is related to the SET methyltransferase domain, and multiple zinc fingers that mediate sequence-specific DNA binding and protein-protein interactions. Prdm factors either act as direct histone methyltransferases or recruit a suite of histone-modifying enzymes to target promoters. In this way, they function in many developmental contexts to drive and maintain cell state transitions and to modify the activity of developmental signalling pathways. Here, we provide an overview of the structure and function of Prdm family members and discuss the roles played by these proteins in stem cells and throughout development.

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Section: Box 2 Prdms In Cancer and Other Diseasesmentioning

confidence: 99%

The Prdm family: expanding roles in stem cells and development

2012

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“…Collectively, our data indicate that EVI1 is a multipurpose transcription factor that synergizes with FOS in invasive tumors. E cotropic viral integration site 1 (EVI1) is a zinc finger (ZNF) transcription factor (TF), and its overexpression in myeloid leukemia (1)(2)(3) and epithelial cancers (1,2,(4)(5)(6)(7)(8)(9) has been extensively studied and correlated with adverse patient outcome (7,10,11). EVI1 also controls several aspects of embryonic development, including hematopoiesis, angiogenesis, and heart and neural development (12).…”

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confidence: 99%

Ecotopic viral integration site 1 (EVI1) regulates multiple cellular processes important for cancer and is a synergistic partner for FOS protein in invasive tumors

Bard-Chapeau

Jeyakani

Kok

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

126

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Ecotropic viral integration site 1 (EVI1) is an oncogenic dual domain zinc finger transcription factor that plays an essential role in the regulation of hematopoietic stem cell renewal, and its overexpression in myeloid leukemia and epithelial cancers is associated with poor patient survival. Despite the discovery of EVI1 in 1988 and its emerging role as a dominant oncogene in various types of cancer, few EVI1 target genes are known. This lack of knowledge has precluded a clear understanding of exactly how EVI1 contributes to cancer. Using a combination of ChIP-Seq and microarray studies in human ovarian carcinoma cells, we show that the two zinc finger domains of EVI1 bind to DNA independently and regulate different sets of target genes. Strikingly, an enriched fraction of EVI1 target genes are cancer genes or genes associated with cancer. We also show that more than 25% of EVI1-occupied genes contain linked EVI1 and activator protein (AP)1 DNA binding sites, and this finding provides evidence for a synergistic cooperative interaction between EVI1 and the AP1 family member FOS in the regulation of cell adhesion, proliferation, and colony formation. An increased number of dual EVI1/AP1 target genes are also differentially regulated in late-stage ovarian carcinomas, further confirming the importance of the functional cooperation between EVI1 and FOS. Collectively, our data indicate that EVI1 is a multipurpose transcription factor that synergizes with FOS in invasive tumors. E cotropic viral integration site 1 (EVI1) is a zinc finger (ZNF) transcription factor (TF), and its overexpression in myeloid leukemia (1-3) and epithelial cancers (1, 2, 4-9) has been extensively studied and correlated with adverse patient outcome (7, 10, 11). EVI1 also controls several aspects of embryonic development, including hematopoiesis, angiogenesis, and heart and neural development (12). Three major alternative splice forms of the MDS1 and EVI1 complex locus (MECOM) locus have been identified, including EVI1, EVI1Δ324, and MDS1-EVI1. The PRDI-BF1 and RIZ homology domain containing Myelodysplastic syndrome (MDS)1-EVI1 isoform acts as a tumor suppressor gene, whereas the shorter isoforms, EVI1 and EVI1Δ324, that lack this domain display oncogenic functions (13). The most oncogenic isoform, EVI1, encodes a 1,051-aa protein containing two DNA binding ZNF domains of seven and three motifs. The N-terminal ZNF domain binds to a GATA-like consensus motif (14), whereas the distal ZNF domain binds to an v-ets erythroblastosis virus E26 oncogene homolog (ETS)-like motif (15). EVI1Δ324 lacks ZNFs motifs 6 and 7, which prevents its binding to GATA-like sites.Despite its discovery in 1988 (16, 17), very few EVI1 target genes have been identified, and most of these loci are known to be bound by EVI1 . This lack of knowledge regarding the genes transcriptionally regulated by EVI1 has precluded a complete understanding of EVI1's role in development and cancer. In general, these biological processes are triggered by gene expression changes coordinate...

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“…Studying the gene expression profile of ependymoma tumor cells with nonneoplastic ependymal cells, Koos et al [17 ] identified the marked overexpression of the transcription factor Evi-1 (ecotropic viral integration site 1). Moreover, they detected MDS1/EVI1 fusion transcripts in half of the ependymomas and could inhibit the growth of primary ependymoma cells with an EVI1-specific siRNA.…”

Section: Prognostic Markersmentioning

confidence: 99%