Researchers reveal important role of estrogen in neuroblastoma

The female sex hormone estrogen can perform an important role in neuroblastoma, a form of cancer mainly affecting young children. In laboratory experiments, researchers at Karolinska Institutet in Sweden demonstrate that estrogen treatment and overexpression of the estrogen receptor cause malignant neuroblastoma cells to mature into neuron-like cells. The study, which is published in PNAS, gives hope of new treatment possibilities.

Neuroblastoma forms in the peripheral nervous system and is one of the most common forms of solid cancer in young children. The disease mainly affects babies and young children, and while in some cases the tumors can disappear of their own accord, the majority are aggressive, metastasizing cancer tumors that are resistant to modern combinations of surgery, radiotherapy and intensive chemotherapy.

The most aggressive forms of neuroblastoma are often associated with a more active MYCN gene, which drives tumor cell growth and spread and inhibits the maturation of the cells.

"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 estrogen receptor ERalpha. The present study shows that the inhibition of these microRNA molecules or estrogen therapy in combination with an overexpression of the estrogen receptor can cause aggressive neuroblastoma cells with MYCN activation to mature into neuron-like cells which behave more like normal cells.

The researchers studied tumor tissue from patients, cultivated human tumor cells and tumors 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 tumor tissue from patients show that those with a high level of the estrogen receptor have a better survival rate that those with a low.

"Our data suggests that estrogen could be a therapeutic method for patients who express high levels of the estrogen receptor," continues Professor 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."