NCYM upregulated N-Myc mRNA expression, NCYM RNA formed a complex with NonO protein, and knocking down NCYM expression reduced neuroblastoma cell proliferation.
However, using four model systems, we showed that long-term silencing of MYCN induces only a small loss of DNA methylation at the RASSF1A promoter in MYCN amplified neuroblastoma cell lines and over-expression of MYCN does not induce any DNA methylation, suggesting that MYCN is not critical for DNA hypermethylation in neuroblastoma.
It is concluded that in situ hybridization of tissue sections is as effective as Southern blot analysis of tumor cell DNA in identifying human neuroblastoma tumors in which the N-myc gene is of prognostic significance.
MIF increased the expression of N-myc mRNA and N-Myc protein and induced N-Myc translocation from the cytoplasm to nucleus in neuroblastoma cell lines.
The N-myc gene, first detected by its homology to the second exon of the c-myc gene, is amplified and/or expressed in tumours or cell lines derived from neuroblastoma, retinoblastoma and SCLC.
We have demonstrated that the entire murine N-myc gene and the sequences necessary for its expression in human neuroblastoma cells are contained within a 7.4-kilobase murine genomic clone.
In addition, MYCN directly increased polyamine synthesis and promoted neuroblastoma cell proliferation by regulating SLC3A2 and other regulatory components of the polyamine pathway.
Here, we demonstrated that the expression levels of LGP2 were either low or undetectable in all NB cell lines tested with or without MYCN amplification.
We performed loss of heterozygosity (LOH) analysis of 120 well characterized NB to better define specific regions of 1p loss and any association with clinical and biological prognostic features (DNA index, MYCN, age, and stage).
The MYCN transcription factor, whose gene is amplified in ∼30% of high-risk neuroblastoma cases, influences drug resistance by regulating a cadre of genes, including those involved with drug efflux, however, other high-risk subtypes of neuroblastoma lacking MYCN amplification, such as those with chromosome 11q deletions, also acquire multidrug resistance.
Four neuroblastoma xenograft samples derived from cell lines with known N-myc gene copy number were also evaluated, as were 7 samples of non-small cell lung cancer (NSCLC) tumors with known Skp2 gene amplification.
Using a zebrafish model of MYCN-overexpressing neuroblastoma, we demonstrate that mutant ptpn11 expression in the adrenal gland analog of MYCN transgenic fish promotes the proliferation of hyperplastic neuroblasts, accelerates neuroblastomagenesis, and increases tumor penetrance.
The involvement of the MYC-MAX-MXD1 network in the development and progression of neural crest cell tumors is further supported by the lack of functional MAX in rat PCC (PC12) cells and by the amplification of MYCN in neuroblastoma and suggests that loss of MAX function is correlated with metastatic potential.
Children diagnosed at age ≥ 18 months with metastatic MYCN-nonamplified neuroblastoma (NBL-NA) are at high risk for disease relapse, whereas those diagnosed at age < 18 months are nearly always cured.
Whereas N-Myc repressed and retinoid activated both TG2 isoforms, repression of TG2-L, but not simultaneous repression of TG2-L and TG2-S, enhanced neuroblastoma cell differentiation due to N-Myc small interfering RNA or retinoid.
Here we discuss the role of MYCN in neuroblastoma with a special focus on the contribution of elevated MYCN signaling for an aggressive and undifferentiated phenotype as well as the potential of using MYCN as a therapeutic target.
High levels of NKAIN2 were detected in the MYCN-amplified NB cell lines and in the most aggressive NB lesions as well as in the peripheral blood of a large cohort of NB patients.