Re-Expression of the Retinoblastoma-Binding Protein 2-Homolog 1 Reveals Tumor-Suppressive Functions in Highly Metastatic Melanoma Cells

Roesch, Alexander; Becker, Bernd; Schneider-Brachert, Wulf; Hagen, Ilja; Landthaler, Míchael; Vogt, Thomas

doi:10.1038/sj.jid.5700324

Cited by 41 publications

(43 citation statements)

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“…Based on the previously found antiproliferative effects of the re-expressed C-term of RBP2-H1 4 and the present transcriptional data on full length RBP2-H1, one could assume that re-establishment of full length RBP2-H1 in melanoma cells may attenuate their malignant potential and re-directs them to a more melanocyte-like state. To prove this hypothesis, we performed functional assays focusing on cellular processes that were predicted by our microarrays to be particularly affected upon RBP2-H1-dependent gene transcription, i.e.…”

Section: Rbp2-h1/jarid1b Binds To a Multitude Of Human Chromosomal Resupporting

confidence: 60%

“…3,4 In brief, 3 3 10 5 human embryonic kidney cells (HEK 293, DMSZ, Braunschweig, Germany) were seeded into 6-well plates and transiently co-transfected at 60% confluence either with (i) pcDNA3.1(2)/RBP2-H1 plus pBIND/GAL4-FOXG1b or (ii) pcDNA3.1(2)/RBP2-H1 plus pBIND/GAL4-PAX9 or (iii) pcDNA3.1(2)/RBP2-H1 plus pBIND/GAL4-LMO2 using Nanofectin TM (PAA, Pasching, Austria) according to the manufacturer's recommendations. Transfected cells were harvested mechanically after 24-hr incubation.…”

Section: Co-immunoprecipitation and Immunoblottingmentioning

confidence: 99%

“…Sample preparation for microarray hybridization was carried out as described in accordance with the Affymetrix GeneChip TM Expression Analysis Technical Manual. 4 One microgram of the total RNA purified with RNeasy TM Mini columns (Qiagen, Hilden, Germany) according to the manufacturer's directions, were used to generate double-stranded cDNA and subsequently biotinlabeled cRNA (MessageAmp II TM , Biotin Enhanced Kit, Ambion). The length of the cRNA products was confirmed using the Agilent 2100 bioanalyzer (Agilent Technologies, Palo Alto, USA).…”

Section: Expression Screening Of Foxg1b Pax9 and Lmo2mentioning

confidence: 99%

“…4 However, since a close RBP2-H1-homolog, PLU-1/JARID1B (98.5% cDNA homology), was recently reported to be a direct transcriptional repressor, 13 we wondered if RBP2-H1 could also directly control gene transcription. A general interaction of RBP2-H1 with genomic DNA could be postulated due to typical sequence motifs, e.g.…”

Section: Rbp2-h1/jarid1b Is a Dna-binding Factor With Direct Transcrimentioning

confidence: 99%

“…1,3 Recently, we showed that RBP2-H1 has a tumor suppressive activity partly due to binding and stabilization of hypophosphorylated retinoblastoma protein (pRb) leading to maintenance of pRb-mediated cell cycle control. 4 As a result of truncation studies, we located the pRb-binding activity of RBP2-H1 to its C-term, containing a homolog region of the non-T/E1A-pRb binding domain known from other retinoblastoma binding proteins like RBP2. 5 Moreover, RBP2-H1 and its splicing variants PLU-1 and RBBP2H1a contain further well-conserved domains known to be involved in direct gene regulation and chromatin homeostasis, e.g.…”

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RBP2‐H1/JARID1B is a transcriptional regulator with a tumor suppressive potential in melanoma cells

Roesch

Mueller²,

Stempfl

et al. 2007

Intl Journal of Cancer

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The RBP2-H1/JARID1B nuclear protein belongs to the ARID family of DNA-binding proteins and is a potential tumor suppressor that is lost during melanoma development. As we have recently shown, one physiological function of RBP2-H1/JARID1B is to exert cell cycle control via maintenance of active retinoblastoma protein. We now add new evidence that RBP2-H1/JARID1B can also directly regulate gene transcription in a reporter assay system, either alone or as part of a multimolecular complex together with the developmental transcription factors FOXG1b and PAX9. In melanoma cells, chromatin immunoprecipitation combined with promoter chip analysis (ChIP-on-chip) suggests a direct binding of re-expressed RBP2-H1/JARID1B to a multitude of human regulatory chromosomal elements (promoters, enhancers and introns). Among those, a set of 23 genes, including the melanoma relevant genes CDK6 and JAG-1 could be confirmed by cDNA microarray analyses to be differentially expressed after RBP2-H1/JARID1B re-expression. In contrast, in nonmelanoma HEK 293 cells, RBP2-H1/JARID1B overexpression only evokes a minor transcriptional response in cDNA microarray analyses. Because the transcriptional regulation in melanoma cells is accompanied by an inhibition of proliferation, an increase in caspase activity and a partial cell cycle arrest in G1/0, our data support an anti-tumorigenic role of RBP2-H1/JARID1B in melanocytic cells. ' 2007 Wiley-Liss, Inc.Key words: melanoma; transcription; gene expression; retinoblastoma protein binding protein; apoptosisIn 1999, our group detected a gene transcript suppressed by UV-B in normal human melanocytes (Acc. No. AF087481, 1 ). Based on its homology to the previously described RBP2, 2 this new gene was termed retinoblastoma binding protein 2-homolog 1 (RBP2-H1). Subsequent expression studies revealed a frequent loss of RBP2-H1 in the majority of advanced and metastatic melanomas in vivo and in many melanoma cell lines, whereas benign melanocytic tumors, normal tissues and other cancer types mostly retain RBP2-H1. 1,3 Recently, we showed that RBP2-H1 has a tumor suppressive activity partly due to binding and stabilization of hypophosphorylated retinoblastoma protein (pRb) leading to maintenance of pRb-mediated cell cycle control. 4 As a result of truncation studies, we located the pRb-binding activity of RBP2-H1 to its C-term, containing a homolog region of the non-T/E1A-pRb binding domain known from other retinoblastoma binding proteins like RBP2. 5 Moreover, RBP2-H1 and its splicing variants PLU-1 and RBBP2H1a contain further well-conserved domains known to be involved in direct gene regulation and chromatin homeostasis, e.g. 3 PHD motifs and the ARID (AT-rich interacting) DNA-binding domain. [6][7][8][9] Although the 3 splicing variants show a cDNA sequence homology of more than 98%, RBP2-H1 differs from PLU-1 and RBBP2H1a by an additional exon encoding a region with strong homology to chromosomal ALU repeats. Thus, previously reported differences in tissue expression (PLU-1 shows a restricted expre...

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Section: Rbp2-h1/jarid1b Binds To a Multitude Of Human Chromosomal Resupporting

confidence: 60%

Section: Co-immunoprecipitation and Immunoblottingmentioning

confidence: 99%

Section: Expression Screening Of Foxg1b Pax9 and Lmo2mentioning

confidence: 99%

Section: Rbp2-h1/jarid1b Is a Dna-binding Factor With Direct Transcrimentioning

confidence: 99%

mentioning

confidence: 99%

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RBP2‐H1/JARID1B is a transcriptional regulator with a tumor suppressive potential in melanoma cells

Roesch

Mueller²,

Stempfl

et al. 2007

Intl Journal of Cancer

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In vivo and ex vivo MR imaging of slowly cycling melanoma cells

Magnitsky¹,

Roesch

Herlyn

et al. 2011

Magnetic Resonance in Med

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Slowly cycling cells are believed to play a critical role in tumor progression and metastatic dissemination. The goal of this study was to develop a method for in vivo detection of slowly cycling cells. To distinguish these cells from more rapidly proliferating cells that constitute the vast majority of cells in tumors, we used the well‐known effect of label dilution due to division of cells with normal cycle and retention of contrast agent in slowly dividing cells. To detect slowly cycling cells, melanoma cells were labeled with iron oxide particles. After labeling, we observed dilution of contrast agent in parallel with cell proliferation in the vast majority of normally cycling cells. A small and distinct subpopulation of iron‐retaining cells was detected by flow cytometry after 20 days of in vitro proliferation. These iron‐retaining cells exhibited high expression of a biological marker of slowly cycling cells, JARID1B. After implantation of labeled cells as xenografts into immunocompromised mice, iron‐retaining cells were detected in vivo and ex vivo by magnetic resonance imaging that was confirmed by Prussian Blue staining. Magnetic resonance imaging detects not only iron retaining melanoma cells but also iron positive macrophages. Proposed method opens up opportunities to image subpopulation of melanoma cells, which is critical for continuous tumor growth. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.

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Epigenetic Regulator Enzymes and Their Implications in Distinct Malignancies

Ganai¹

2020

Histone Deacetylase Inhibitors in Combinatorial Anticancer Therapy

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Re-Expression of the Retinoblastoma-Binding Protein 2-Homolog 1 Reveals Tumor-Suppressive Functions in Highly Metastatic Melanoma Cells

Cited by 41 publications

References 42 publications

RBP2‐H1/JARID1B is a transcriptional regulator with a tumor suppressive potential in melanoma cells

RBP2‐H1/JARID1B is a transcriptional regulator with a tumor suppressive potential in melanoma cells

In vivo and ex vivo MR imaging of slowly cycling melanoma cells

Epigenetic Regulator Enzymes and Their Implications in Distinct Malignancies

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