“Our research focuses particularly on the activity of this gene and how it relates to neuroblastoma,” says Professor Marie Arsenian-Henriksson at the Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet. “MYCN is often seen only as a marker for a poor prognosis, but it’s critical to the disease and is a possible target for new drugs.” In a previous study, her group discovered that activation of MYCN results in the formation of specific microRNAs, which are relatively small RNA molecules that regulate proteins. Some of these microRNAs disable the oestrogen receptor ERalpha. The present study shows that the inhibition of these microRNA molecules or oestrogen therapy in combination with an overexpression of the oestrogen receptor can cause aggressive neuroblastoma cells with MYCN activation to mature into neuron-like cells which behave more like normal cells. The researchers studied tumour tissue from patients, cultivated human tumour cells and tumours in mouse models for neuroblastoma. In the mice, the neuron-like cells did not grow as quickly as the original cancer cells, and analyses of the tumour tissue from patients show that those with a high level of the oestrogen receptor have a better survival rate that those with a low. “Our data suggests that oestrogen could be a therapeutic method for patients who express high levels of the oestrogen receptor,” continues Professor Arsenian-Henriksson. “Another possible therapy could involve deregulating MYCN or upregulating the oestrogen receptor and then treating with oestrogen. We have previously shown that the deregulation of MYCN leads to a high expression of the oestrogen receptor.” The study was financed by the Lars Hierta Memorial Foundation, the Mary Béve Foundation for Childhood Cancer Research, the Anna-Brita and Bo Castegren Memorial Foundation, the Swedish Cancer Society, the Swedish Research Council, the Swedish Childhood Cancer Foundation, the King Gustaf V’s Jubilee Fund and Karolinska Institutet.
