These results suggest the following: (a) the primary tumor had a least two clones; (b) the rearrangement interrupted N-myc gene expression; and (c) oncogenesis preceded N-myc gene amplification.
The availability of an ARMS cell line that harbors the t(1;13)(p36;q14) constitutes a useful tool for further understanding the role of the PAX7-FKHR fusion gene in RMS oncogenesis and may improve knowledge of the possible relation between PAX7-FKHR and MYCN amplification.
We speculate that N-Myc repression of beta1 integrin expression leads to a less differentiated phenotype, resulting in increased growth and tumorigenesis if properly supported or apoptosis if deprived of growth sustaining molecules.
These data suggest that inappropriate perinatal MycN expression in paravertebral ganglia cells from TH-MYCN mice initiated tumorigenesis by altering the physiologic process of neural crest cell deletion.
MYCN deregulation is a feature of rhabdomyosarcoma tumorigenesis, defines groups of patients with a poor prognosis, and is a potential target for novel therapies.
Finally, HMGA1 repression by RNA interference reduced neuroblastoma cell proliferation, indicating that HMGA1 is a novel MYCN target gene relevant for neuroblastoma tumorigenesis.
These findings establish a mechanistic link between N-Myc and death receptor machinery, which may serve as a checkpoint to guard the cell from N-Myc-initiated tumorigenesis.
Thus these data support that MYCN oncogene gain/overexpression accompanied by reduced expression of BIN1 tumor suppressor may contribute to central neurocytoma tumorigenesis.
Although it has been suggested that the MYCN oncoprotein functions may influence tumorigenesis and patient survival in neuroblastoma, the mechanism of these functions remains unclear.
This work implicates polyamine biosynthesis as an arbiter of MYCNoncogenesis and shows initial efficacy for polyamine depletion strategies in neuroblastoma, a strategy that may have utility for this and other MYC-driven embryonal tumors.
We used the TH-MYCN transgenic murine model to examine the role of p53-driven apoptosis on neuroblastoma tumorigenesis and the response to chemotherapy.
In conclusion, we identified a selected set of biologically relevant genes modulated by PAX3-FKHR, and demonstrated that PAX3-FKHR contributes to the expression of MYCN and in turn MYCN collaborates with PAX3-FKHR in tumorigenesis.
We hypothesize that MDM2 contributes to MYCN-driven tumorigenesis helping to ameliorate p53-dependent apoptotic oncogenic stress during tumor initiation and progression.
Our results uncover a widespread correlation between miRNA activation and c-MYC/MYCN-mediated coding gene expression modulation and further substantiate the overlapping functions of c-MYC and MYCN in the process of tumorigenesis.
Overexpression of the N-Myc transcription factor, an oncogene frequently amplified in neuroblastoma, induced miR-421 expression, which, in turn, down-regulated ATM expression, establishing a linear signaling pathway that may contribute to N-Myc-induced tumorigenesis in neuroblastoma.
In an attempt to understand the molecular mechanism of meningioma recurrence we investigated the N-Myc downstream-regulated gene 2 (NDRG2), which has recently been described as important in suppressing cellular carcinogenesis in different types of cancer.