Regulation of MYCNexpression in human neuroblastoma cellsReport as inadecuate




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BMC Cancer

, 9:239

First Online: 18 July 2009Received: 08 January 2009Accepted: 18 July 2009DOI: 10.1186-1471-2407-9-239

Cite this article as: Jacobs, J.F., van Bokhoven, H., van Leeuwen, F.N. et al. BMC Cancer 2009 9: 239. doi:10.1186-1471-2407-9-239

Abstract

BackgroundAmplification of the MYCN gene in neuroblastoma NB is associated with a poor prognosis. However, MYCN-amplification does not automatically result in higher expression of MYCN in children with NB. We hypothesized that the discrepancy between MYCN gene expression and prognosis in these children might be explained by the expression of either MYCN-opposite strand MYCNOS or the shortened MYCN-isoform ΔMYCN that was recently identified in fetal tissues. Both MYCNOS and ΔMYCN are potential inhibitors of MYCN either at the mRNA or at the protein level.

MethodsExpression of MYCN, MYCNOS and ΔMYCN was measured in human NB tissues of different stages. Transcript levels were quantified using a real-time reverse transcriptase polymerase chain reaction assay QPCR. In addition, relative expression of these three transcripts was compared to the number of MYCN copies, which was determined by genomic real-time PCR gQPCR.

ResultsBoth ΔMYCN and MYCNOS are expressed in all NBs examined. In NBs with MYCN-amplification, these transcripts are significantly higher expressed. The ratio of MYCN:ΔMYCN expression was identical in all tested NBs. This indicates that ΔMYCN and MYCN are co-regulated, which suggests that ΔMYCN is not a regulator of MYCN in NB. However, the ratio of MYCNOS:MYCN expression is directly correlated with NB disease stage p = 0.007. In the more advanced NB stages and NBs with MYCN-amplification, relatively more MYCNOS is present as compared to MYCN. Expression of the antisense gene MYCNOS might be relevant to the progression of NB, potentially by directly inhibiting MYCN transcription by transcriptional interference at the DNA level.

ConclusionThe MYCNOS:MYCN-ratio in NBs is significantly correlated with both MYCN-amplification and NB-stage. Our data indicate that in NB, MYCN expression levels might be influenced by MYCNOS but not by ΔMYCN.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-9-239 contains supplementary material, which is available to authorized users.

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Author: Joannes FM Jacobs - Hans van Bokhoven - Frank N van Leeuwen - Christina A Hulsbergen-van de Kaa - I Jolanda M de Vries -

Source: https://link.springer.com/







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