Transcription factor activating protein 2 beta (TFAP2B) mediates noradrenergic neuronal differentiation in neuroblastoma

Ikram, Fakhera; Ackermann, Sandra; Kahlert, Yvonne; Volland, Ruth; Roels, Frederik; Engesser, Anne; Hertwig, Falk; Kocak, H; Hero, Barbara; Dreidax, Daniel; Henrich, Kai-Oliver; Berthold, Frank; Nürnberg, Peter; Westermann, Frank; Fischer, Matthias

doi:10.1016/j.molonc.2015.10.020

Cited by 37 publications

(65 citation statements)

References 54 publications

(60 reference statements)

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“…Induction of fibronectin (FN1), as well as the EMT transcription factors SNAI1, SNAI2, TWIST1 and TWIST2 was apparent in SK-N-BE(2)-C cells 24 hours after Wnt3A/Rspo2 treatment ( Figure 3C). Analysis of genes that are increased with retinoic acid induced differentiation of neuroblastoma cells (NGRF, NF68, NTRK1, SYP, MAP2, NEFM, DKK2) [44][45][46] showed that all were elevated after 72 hours Wnt3a/Rspo2 treatment. Downregulation of ASCL1 was also observed ( Figure 3D).…”

Section: Immunoblotting and Immunohistochemistrymentioning

confidence: 99%

Wnt signalling drives context-dependent differentiation or proliferation in neuroblastoma

Szemes

Greenhough

Melegh

et al. 2018

Preprint

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Neuroblastoma is one of the commonest and deadliest solid tumours of childhood, and is thought to result from disrupted differentiation of the developing sympathoadrenergic lineage of the neural crest. Neuroblastoma exhibits intra-and intertumoural heterogeneity, with high risk tumours characterised by poor differentiation, which can be attributable to MYCN-mediated repression of genes involved in neuronal differentiation. MYCN is known to co-operate with oncogenic signalling pathways such as Alk, Akt and MEK/ERK signalling, and, together with c-MYC has been shown to be activated by Wnt signalling in various tissues. However, our previous work demonstrated that Wnt3a/Rspo2 treatment of some neuroblastoma cell lines can, paradoxically, decrease c-MYC and MYCN proteins.This prompted us to define the neuroblastoma-specific Wnt3a/Rspo2-driven transcriptome using RNA sequencing, and characterise the accompanying changes in cell biology.Here we report the identification of ninety Wnt target genes, and show that Wnt

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Section: Immunoblotting and Immunohistochemistrymentioning

confidence: 99%

Wnt signalling drives context-dependent differentiation or proliferation in neuroblastoma

Szemes

Greenhough

Melegh

et al. 2018

Preprint

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“…7 More recently, TFAP2B has been implicated in neoplastic diseases. [8][9][10][11][12] TFAP2B is overexpressed in alveolar rhabdomyosarcoma (aRMS), a rare childhood malignancy. 8 Approximately 80% of aRMSs harbor translocations t (2;13) or t (1;13), which juxtapose the PAX3 or PAX7 gene with FOXO1.…”

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confidence: 99%

Lobular carcinoma in situ and invasive lobular breast cancer are characterized by enhanced expression of transcription factor AP-2β

Raap

Gronewold

Christgen

et al. 2018

Laboratory Investigation

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Transcription factor AP-2β (TFAP2B) regulates embryonic organ development and is overexpressed in alveolar rhabdomyosarcoma, a rare childhood malignancy. Gene expression profiling has implicated AP-2β in breast cancer (BC). This study characterizes AP-2β expression in the mammary gland and in BC. AP-2β protein expression was assessed in the normal mammary gland epithelium, in various reactive, metaplastic and pre-invasive neoplastic lesions and in two clinical BC cohorts comprising >2000 patients. BCs from various genetically engineered mouse (GEM) models were also evaluated. Human BC cell lines served as functional models to study siRNA-mediated inhibition of AP-2β. The normal mammary gland epithelium showed scattered AP-2β-positive cells in the luminal cell layer. Various reactive and pre-invasive neoplastic lesions, including apocrine metaplasia, usual ductal hyperplasia and lobular carcinoma in situ (LCIS) showed enhanced AP-2β expression. Cases of ductal carcinoma in situ (DCIS) were more often AP-2β-negative (P<0.001). In invasive BC cohorts, AP-2β-positivity was associated with the lobular BC subtype (P<0.001), loss of E-cadherin (P<0.001), a positive estrogen receptor (ER) status (P<0.001), low Ki67 (P<0.001), low/intermediate Oncotype DX recurrence scores (P<0.001), and prolonged event-free survival (P=0.003). BCs from GEM models were all AP-2β-negative. In human BC cell lines, AP-2β expression was independent from ER-signaling. SiRNA-mediated inhibition of AP-2β diminished proliferation of lobular BC cell lines in vitro. In summary, AP-2β is a new mammary epithelial differentiation marker. Its expression is preferentially retained and enhanced in LCIS and invasive lobular BC and has prognostic implications. Our findings indicate that AP-2β controls tumor cell proliferation in this slow-growing BC subtype.

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“…The disruption of the TFAP2B motif is also interesting because the TFAP2B transcription factor is highly expressed in migrating neural crest cells which are involved in the development of the sympathetic nervous system and are likely cells of origin for NB[35]. In addition, low TFAP2B expression is associated with poor survival and prevents neuronal differentiation of NB cells in vitro via downregulation of MYCN and REST[36]. Our results indicate that TFAP2B may also downregulate KDM5B .…”

Section: Discussionmentioning

confidence: 95%

BreakCA, a method to discover indels using ChIP-seq and ATAC-seq reads, finds recurrent indels in regulatory regions of neuroblastoma genomes

Sen

Tyndale

et al. 2019

Preprint

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10Most known cancer driver mutations are within protein coding regions of the genome, however, there are 11 several important examples of oncogenic non-coding regulatory mutations. We developed a method to 12 identify insertions and deletions (indels) in regulatory regions using aligned reads from chromatin 13 immunoprecipitation followed by sequencing (ChIP-seq) or the assay for transposase-accessible 14 chromatin (ATAC-seq). Our method, which we call BreakCA for Breaks in Chromatin Accessible 15 regions, allows non-coding indels to be discovered in the absence of whole genome sequencing data, out-16 performs popular variant callers such as the GATK-HaplotypeCaller and VarScan2, and detects known 17 oncogenic regulatory mutations in T-cell acute lymphoblastic leukemia cell lines. We apply BreakCA to 18 identify indels in H3K27ac ChIP-seq peaks in 23 neuroblastoma cell lines and, after removing common 19 germline variants, we identify 23 rare germline or somatic indels that occur in multiple neuroblastoma 20 cell lines. Among them, 4 indels are candidate oncogenic drivers that are present in 4 or 5 cell lines, 21 absent from the genome aggregation database of over 15,000 whole genome sequences, and within the 22 promoters or first introns of known genes (PHF21A, ADAMTS19, GPR85 and RALGDS). In addition, we 23

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Transcription factor activating protein 2 beta (TFAP2B) mediates noradrenergic neuronal differentiation in neuroblastoma

Cited by 37 publications

References 54 publications

Wnt signalling drives context-dependent differentiation or proliferation in neuroblastoma

Wnt signalling drives context-dependent differentiation or proliferation in neuroblastoma

Lobular carcinoma in situ and invasive lobular breast cancer are characterized by enhanced expression of transcription factor AP-2β

BreakCA, a method to discover indels using ChIP-seq and ATAC-seq reads, finds recurrent indels in regulatory regions of neuroblastoma genomes

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