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'Key breast cancer molecule found'

Tuesday 25 August 2009

“Millions of lives could be saved by a groundbreaking discovery that has found a way to stop tumours growing and spreading,” according to the front page of the Daily Express . Scientists have found out how breast cancer cells “turn off” microRNA molecules, allowing cancer to spread, and are working on a drug based on their findings, says the Daily Express ' article on breast cancer.

The complex research behind this story has helped to explain how the hormone oestrogen affects breast cancer cells. This research did not aim to develop a new treatment for breast cancer, and did not specifically look at tumour growth or spreading, but may add to our understanding of the biology of cancer and help to identify new ways of treating it. More research will be needed to investigate further the role of microRNAs in breast cancer, and to determine whether new treatments targeting or imitating these molecules are likely to be useful. It is too early in this process to know whether talk of a “cure” based on these findings is realistic.

Where did the story come from?

This research into oestrogen and breast cancer cells was conducted by Dr Leandro Castellano and colleagues from Imperial College London and the Howard Hughes Medical Institute in the US. The study was funded by the Breast Cancer Campaign charitable fund and published in the peer-reviewed medical journal Proceedings of the National Academy of Sciences of the USA .

What kind of scientific study was this?

This was a laboratory study using genetic techniques to look at how the hormone oestrogen affects breast cancer cells.

Within the body’s cells, oestrogen molecules bind to proteins called oestrogen receptors to form a ‘complex’ that can bind to DNA and affect which genes are switched on. The researchers thought that oestrogen might also affect the production of small pieces of genetic material called microRNAs. MicroRNAs are short strands of ribonucleic acid (RNA), similar in structure to DNA, that are involved in regulating how genes work. Unlike the ‘messenger’ form of RNA they do not contain instructions for producing proteins themselves.

In order to find out whether oestrogen affected the production of microRNA, the researchers treated breast cancer cells with oestrogen and assessed how this affected the levels of a range of different microRNA molecules. These results were compared to those from breast cancer cells that had been genetically engineered to prevent oestrogen having an effect. They then carried out further experiments to confirm whether the microRNAs identified were being regulated by oestrogen in the breast cancer cells.

The researchers then compared the levels of the microRNAs in samples of breast cancer tissue both with and without high levels of the oestrogen receptor protein (called oestrogen receptor positive and negative respectively). They also looked at whether these microRNAs would be able to regulate the production of oestrogen receptors and of proteins that work with the oestrogen receptor.

What were the results of the study?

The researchers identified a range of microRNA strands that were affected by oestrogen. These microRNAs came from three different microRNA clusters, which are groups of microRNAs made into one long strand. This strand undergoes processing within the cell, firstly to produce individual precursor microRNAs and then later to produce mature microRNAs.

The researchers mainly focused on one cluster (called mir-17-92) that is produced from instructions found on the long arm of chromosome 13. Previous research had suggested that this area of chromosome 13 was involved in breast cancer, and that the mir-17-92 microRNA cluster has been implicated in lung cancer and lymphoma blood cancer.

The researchers confirmed that production of the mir-17-92 cluster of microRNAs was being switched on by oestrogen. They also showed that production of the mir-17-92 cluster was higher in breast cancer tissue that had higher levels of oestrogen receptor proteins. One of the precursor microRNAs made from this cluster (called pre-miR-18a) was produced in larger amounts in oestrogen-receptor-positive breast cancer tissue than in oestrogen-receptor negative breast cancer tissue, but levels of the mature microRNA (called miR-18a) did not differ.

The microRNAs produced from the mir-17-92 and other two clusters identified were shown to “turn down” the production of the oestrogen receptor and related proteins.

What interpretations did the researchers draw from these results?

The researchers suggest that the mir-17-92 cluster acts as a tumour suppressor in breast cancer. They say that this is the first time research has identified a role for microRNAs in the process by which oestrogen receptors regulate their own production within breast cancer cells in response to oestrogen.

What does the NHS Knowledge Service make of this study?

This complex research has shed more light on the effect that oestrogen can have on breast cancer cells. Although this research did not aim to develop a new treatment for breast cancer, work that improves our understanding of the biology of cancer can help to identify new ways of treating it.

More research will be needed to investigate further the role of microRNAs in breast cancer in order to determine whether treatments that target or imitate these molecules are likely to be useful. This research is welcome as the initial step towards understanding this relatively unexplored aspect of breast cancer. However, despite what some news coverage may suggest, the work does not yet demonstrate a cure for this, or any other, type of cancer.

Analysis by Bazian
Edited by NHS Website

Links to the headlines

Scientists two years from developing 'potential cure' for breast cancer

The Daily Telegraph, 25 August 2009

Scientists 'close to breast cancer cure' after British researchers find a way to stop tumours growing

Daily Mail, 25 August 2009

Breast cancer breakthrough

Daily Express, 24 August 2009

Links to the science

Castellano L, Giamas G, Jacob J et al.

The estrogen receptor-α-induced microRNA signature regulates itself and its transcriptional response

PNAS, Published online before print August 24 2009