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p53 is a direct transcriptional target of MYCN in neuroblastoma.
MYCN amplification occurs in approximately 25% of neuroblastomas, where it is associated with rapid tumor progression and poor prognosis. MYCN plays a paradoxical role in driving cellular… Expand
Cell Cycle Regulation Targets of MYCN Identified by Gene Expression Microarrays
Background: We have previously shown that MYCN knockdown causes a G1 arrest in MYCN amplified (MNA), p53 wild type (wt) and p53 mutant MNA neuroblastoma cell lines, with increases in p21WAF1 and hypo… Expand
High Frequency of p53/MDM2/p14ARF Pathway Abnormalities in Relapsed Neuroblastoma
- J. Carr-Wilkinson, K. O'Toole, +12 authors D. Tweddle
- Biology, Medicine
- Clinical Cancer Research
- 9 February 2010
Purpose: Most neuroblastomas initially respond to therapy but many relapse with chemoresistant disease. p53 mutations are rare in diagnostic neuroblastomas, but we have previously reported… Expand
Evidence for the development of p53 mutations after cytotoxic therapy in a neuroblastoma cell line.
p53 mutations are rare in neuroblastomas at diagnosis perhaps accounting for their initial response to therapy, but advanced neuroblastoma frequently relapses, and it is possible that p53 mutations… Expand
MYCN oncoprotein targets and their therapeutic potential.
- E. Bell, L. Chen, T. Liu, G. Marshall, J. Lunec, D. Tweddle
- Biology, Medicine
- Cancer letters
- 28 July 2010
The MYCN oncogene encodes a transcription factor which is amplified in up to 40% of high risk neuroblastomas. MYCN amplification is a well-established poor prognostic marker in neuroblastoma, however… Expand
Identification of candidate genes involved in neuroblastoma progression by combining genomic and expression microarrays with survival data
Identifying genes, whose expression is consistently altered by chromosomal gains or losses, is an important step in defining genes of biological relevance in a wide variety of tumour types. However,… Expand
MYCN sensitizes neuroblastoma to the MDM2-p53 antagonists Nutlin-3 and MI-63
MYCN amplification is a major biomarker of poor prognosis, occurring in 25–30% of neuroblastomas. MYCN has contradictory roles in promoting cell growth and sensitizing cells to apoptosis. We have… Expand
MDM2-p53 interaction in paediatric solid tumours: preclinical rationale, biomarkers and resistance.
p53 is one of the main regulators of apoptosis, senescence, cell cycle arrest and DNA repair. The expression, function and stabilization of p53 are governed by a complex network of regulators… Expand
The p53 pathway and its inactivation in neuroblastoma.
Early studies of p53 in neuroblastoma reported infrequent mutations in tumours and cell lines. Cytoplasmic sequestration was later proposed as an alternative mechanism of inactivation, but many… Expand
Increased frequency of aberrations in the p53/MDM2/p14(ARF) pathway in neuroblastoma cell lines established at relapse.
p53 mutations have been reported in cell lines derived from relapsed neuroblastoma tumors. We hypothesize that functional inactivation of p53 by mutation or other mechanisms is common in relapsed… Expand