In vivoregulation of single copy and amplified N-myc in human neuroblastoma cells

Lutz, W; Schwab, Manfred

doi:10.1038/sj.onc.1201195

Cited by 46 publications

(42 citation statements)

References 41 publications

(44 reference statements)

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“…Indeed, using chromatin immunoprecipitation, we did not detect methylation of histone H3 at Lys-9, a histone modification associated with heterochromatin, at the MYCN promoter in SH-EP cells (data not shown). Furthermore, by using in vivo footprinting, we previously did not detect proteins at the E2F binding sites in SH-EP cells (19). This observation also excludes competitive binding of a repressor protein in the vicinity of the E2F binding site as a reason for the inability of E2F to bind to the silent MYCN promoter.…”

Section: Discussionmentioning

confidence: 72%

“…Previous in vivo-footprinting experiments did not provide evidence for the presence of repressive proteins at or near the E2F binding sites of the MYCN promoter in SH-EP cells (19). Alternatively, a nucleosome positioned over the E2F binding sites might prevent binding of E2F to the MYCN promoter.…”

Section: E2f-1 Cannot Bind the Promoter Of A Transcriptionally Inactimentioning

confidence: 87%

“…SY5Y cells were obtained from American Type Culture Collection. Neuroblastoma cell lines were cultured as described (19). Drosophila Schneider cells were cultured and transfected as described (29).…”

Section: Methodsmentioning

confidence: 99%

“…A Cdk2-specific antibody was used to control for equal loading. Most of the luciferase reporter constructs have been described (19). The mutation in CT-box 1 was introduced into the wild-type reporter construct using the QuikChange kit (Stratagene).…”

Section: Methodsmentioning

confidence: 99%

“…One of these, a non-consensus binding site, the CT-box, was previously implicated in MYCN regulation based upon in vivo footprinting data (19). Sp1 and the closely related protein Sp3 are the major GC-box binding activities in nuclear extracts from most mammalian cells (for a review, see Refs.…”

mentioning

confidence: 99%

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E2F and Sp1/Sp3 Synergize but Are Not Sufficient to Activate the MYCN Gene in Neuroblastomas

Kramps

Strieder

Sapetschnig

et al. 2004

Journal of Biological Chemistry

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The transcription factors encoded by the MYC genes control diverse tumorigenesis-relevant processes such as cell-cycle progression, growth factor dependence, and response to anti-mitogenic signals (for a review, see Refs. 1 and 2). Overexpression of one of the MYC genes as a result of chromosomal translocation, gene amplification, or loss of negative transcriptional control plays a prominent role in the etiology of many types of tumors (for a review, see Refs. 3 and 4). The MYCN gene is found amplified in several tumors of mostly neuroendocrine origin including about 25% of neuroblastomas, the most common solid tumor in childhood (for a review, see Refs. 5 and 6). Whereas many neuroblastomas regress spontaneously or can be cured with minimal therapy, MYCN-amplified tumors have a poor prognosis. The treatment of these patients has not improved significantly in the course of the last two decades. Recently, the comparison of the gene expression profiles of MYCN-expressing versus non-expressing neuroblastoma cells as well as MYCNamplified versus non-amplified primary tumors have begun to address the functional consequences of the massive overexpression of MYCN resulting from gene amplification (7,8).Several mouse models of Myc-induced tumorigenesis suggest that Myc is not only required for the initiation but also for the maintenance of the tumorigenic state supporting the value of the MYC genes as targets of tumor therapy (9 -11). Roughly half of the drugs that are in clinical use currently act as inhibitors of enzymes. In transcriptional regulation, enzymes are involved mainly as components of signal transduction cascades that relay information to the promoter and as transcriptional co-regulators that modulate local chromatin structure either by covalent modification of histones or by an ATPase-dependent remodeling of nucleosomes (for a review, see Ref. 12). The efficacy of histone deacetylase inhibitors against leukemia has proven the principle of treating cancer by the selective pharmacological modulation of the transcription machinery (13). Application of this concept to the MYCN gene requires a detailed knowledge of the molecular basis of the transcriptional activation of MYCN in neuroblastomas.Toward this goal, we have recently identified the activating members of the E2F family of transcription factors (E2F-1, E2F-2, and E2F-3) as regulators of MYCN expression in neuroblastomas (14). E2F proteins are important regulators of cell-cycle progression, and their activity is negatively controlled by the p16/Rb pathway, which is inactivated in the majority of human cancers (for a review, see Refs. 15 and 16). Although genetic defects of the p16/Rb pathway are rare in neuroblastomas, there is some evidence for a loss of normal control of E2F activity in neuroblastomas by epigenetic means (17).In addition to E2F binding sites, the MYCN promoter contains several putative binding sites for Sp1 and related zinc finger transcription factors (18). One of these, a non-consensus binding site, the CT-box, was previously impli...

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Section: Discussionmentioning

confidence: 72%

Section: E2f-1 Cannot Bind the Promoter Of A Transcriptionally Inactimentioning

confidence: 87%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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E2F and Sp1/Sp3 Synergize but Are Not Sufficient to Activate the MYCN Gene in Neuroblastomas

Kramps

Strieder

Sapetschnig

et al. 2004

Journal of Biological Chemistry

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Amplification of oncogenes in human cancer cells

1998

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Two-dimensional DNA electrophoresis identifies novel CpG islands frequently coamplified withMYCN in neuroblastoma

Wimmer

Zhu

Lamb

et al. 2001

Med. Pediatr. Oncol.

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We report here the identification and cloning of two additional CpG islands that are amplified in neuroblastoma. One contains a sequence that is identical to the first intron of DDX1. The other represents a novel CpG island that is associated with an as yet unidentified gene. We show that the novel CpG island is located in close proximity to the MYCN locus on chromosome 2 and is as frequently coamplified with MYCN in neuroblastoma as NAG and DDX1.

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In vivoregulation of single copy and amplified N-myc in human neuroblastoma cells

Cited by 46 publications

References 41 publications

E2F and Sp1/Sp3 Synergize but Are Not Sufficient to Activate the MYCN Gene in Neuroblastomas

E2F and Sp1/Sp3 Synergize but Are Not Sufficient to Activate the MYCN Gene in Neuroblastomas

Amplification of oncogenes in human cancer cells

Two-dimensional DNA electrophoresis identifies novel CpG islands frequently coamplified withMYCN in neuroblastoma

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