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Estrogen causes neuroblastoma cells to mature into neurons

Date:
January 29, 2018
Source:
Karolinska Institutet
Summary:
The female sex hormone estrogen can perform an important role in neuroblastoma, a form of cancer mainly affecting young children. In laboratory experiments, researchers demonstrate that estrogen treatment and overexpression of the estrogen receptor cause malignant neuroblastoma cells to mature into neuron-like cells. The studygives hope of new treatment possibilities.
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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 tumours can disappear of their own accord, the majority are aggressive, metastasising cancer tumours 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 tumour 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 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 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."

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.


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Materials provided by Karolinska Institutet. Note: Content may be edited for style and length.


Journal Reference:

  1. Johanna Dzieran, Aida Rodriguez Garcia, Ulrica Kristina Westermark, Aine Brigette Henley, Elena Eyre Sánchez, Catarina Träger, Henrik Johan Johansson, Janne Lehtiö, Marie Arsenian-Henriksson. MYCN-amplified neuroblastoma maintains an aggressive and undifferentiated phenotype by deregulation of estrogen and NGF signaling. Proceedings of the National Academy of Sciences, 2018; 201710901 DOI: 10.1073/pnas.1710901115

Cite This Page:

Karolinska Institutet. "Estrogen causes neuroblastoma cells to mature into neurons." ScienceDaily. ScienceDaily, 29 January 2018. <www.sciencedaily.com/releases/2018/01/180129092930.htm>.
Karolinska Institutet. (2018, January 29). Estrogen causes neuroblastoma cells to mature into neurons. ScienceDaily. Retrieved March 2, 2024 from www.sciencedaily.com/releases/2018/01/180129092930.htm
Karolinska Institutet. "Estrogen causes neuroblastoma cells to mature into neurons." ScienceDaily. www.sciencedaily.com/releases/2018/01/180129092930.htm (accessed March 2, 2024).

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