New work from the Karolinska Institutet shows that malignant neuroblastoma cells can mature into neuron-like cells by overexpressing the estrogen receptor and providing an estrogen treatment. The study was published recently in Proceedings of the National Academy of Sciences.
The most aggressive forms of neuroblastoma are often associated with a more active MYCN gene, a driver of tumor cell growth and spread. Marie Arsenian-Henriksson says, "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."
Previously, Arsenian-Henriksson's group found that the activation of MYCN led to the formation of microRNAs that disable ERalpha, the estrogen receptor. In this study, the scientists found that by inhibiting these microRNAs, neuroblastoma cells with MYCN activation could mature into neuron-like cells, which behaved more like normal cells. They also found that an estrogen therapy in combination with an overexpression of the estrogen receptor could lead to the same result. Lastly, in their neuroblastoma mouse model, the scientists found that those that had a high level of the estrogen receptor had a better survival rate than those that didn't.
"Our data suggests that estrogen could be a therapeutic method for patients who express high levels of the estrogen receptor," continues Arsenian-Henriksson. "Another possible therapy could involve deregulating MYCN or upregulating the estrogen receptor and then treating with estrogen. We have previously shown that the deregulation of MYCN leads to a high expression of the estrogen receptor."