UK Scientists Identify Gene's Key Role In Breast Cancer Development

Main Category: Breast Cancer
Also Included In: Cancer / Oncology;  Genetics
Article Date: 30 Aug 2007 - 1:00 PDT

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Breakthrough Breast Cancer scientists have helped identify a critical role for a gene called Tip60 in breast cancer. The research, to be published in the scientific journal Nature on Thursday 30 August, shows for the first time that Tip60 is linked to breast cancer development, and is associated with more aggressive forms of the disease.

The team, at The Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research in London, studied the Tip60 gene in breast biopsies. They discovered that the activity of this gene is significantly lower in breast cancer tissue compared with normal breast tissue. This discovery could have important implications for how some breast cancers are treated in the future.

Breakthrough's scientists, collaborating with a team in Italy, found that defects in this gene seem to appear at an early stage of breast cancer development, and are associated with aggressive cancers that are currently difficult to treat. Tip60 is a tumour suppressor gene, which helps to hold the growth of cells in check, and protects their DNA. Reduced activity of Tip60 contributes to uncontrolled cell growth, which allows breast cancers to develop. Unusually, they found that the reduced levels of Tip60 were caused by only one faulty copy of the gene.

Dr Nelofer Syed, Post-Doctoral scientist at The Breakthrough Breast Cancer Research Centre, said:

"When we are born we inherit two copies of each gene, one each from our mother and father. Typically with tumour suppressor genes, both copies must be faulty for their function to be lost, but we have demonstrated that the Tip60 gene stops working if only one copy is altered. This gives us a real insight into how some breast cancers develop."

Importantly, scientists found lower levels of Tip60 activity to be associated with more aggressive tumours. These findings will have important implications for how some breast cancers are treated in the future

Dr Tim Crook, Team Leader at The Breakthrough Breast Cancer Research Centre and Medical Oncologist, said;

"More aggressive types of breast cancers tend to recur after treatment, spread to other parts of the body and respond less well to chemotherapy. The identification of Tip60's role in breast cancer is a step towards predicting the aggressiveness of the disease and then individualising chemotherapy for women. If we can transfer this knowledge to the clinic, it could have dramatic effects."

The discovery of this link marks an important step forward in our understanding of the genes involved in breast cancer. Further studies will focus on how the gene could be used by doctors to predict how an individual's breast cancer is likely to behave. This will help to ensure that women receive the best treatment possible for their particular breast cancer.

This research is just one example of the groundbreaking work taking place at The Breakthrough Breast Cancer Research Centre. One area of the centre's work is to identify genetic changes that take place in breast cancer cells and use this knowledge to benefit patients in the clinic. For more information about Breakthrough Breast Cancer's research work, please visit http://www.breakthroughcentre.org.uk.

* Tip60 stands for TATT interacting protein of size 60kDa. It is a tumour suppressor gene, initially identified because it binds to a protein made by the Human Immunodeficiency virus (HIV).

* Activity of the Tip60 gene was found to be lower in nearly half of all ductal breast cancers studied (21 of 52 cases) and in 17 out of 20 of tumours classed as 'high grade'

* The amount of TIP60 protein was studied in an additional 179 breast cancer samples. In almost three quarters of these (129/179), there was no TIP60 protein present in the cells' nucleus - in healthy cells this is where most of it is located. The proportion of cancers lacking nuclear TIP60 was even higher when they singled-out aggressive cancers and early cancers - suggesting that this is an early event in breast cancer development.

* This research was conducted by scientists from The Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research in London, with the help of a team of scientists in Italy.

* In the UK, Dr. Nelofer Syed, a Post-Doctoral scientist, and Dr. Tim Crook, Team Leader of the Cancer Genetics and Epigenetics Laboratory at the Breakthrough Research Centre and Medical Oncologist, were both involved in the research.

* In Italy, scientists from the laboratory of Dr Bruno Amati in Milan have shown that Tip60 participates in the response of cells to DNA damage and that this is critical in the maintenance of normal genetic structure.

Breakthrough Breast Cancer:

* Breakthrough Breast Cancer is the UK's leading charity committed to fighting breast cancer through research, campaigning and education. Our essence comes from the thousands of people who are committed to a single vision - to work for a future free from the fear of breast cancer. More information can be found at: http://www.breakthroughcentre.org.uk.

* Breakthrough Breast Cancer in partnership with The Institute of Cancer Research has established the UK's first dedicated breast cancer research centre - The Breakthrough Toby Robins Breast Cancer Research Centre.

* The Breakthrough Toby Robins Breast Cancer Research Centre is situated in the Mary-Jean Mitchell Green Building at the Chester Beatty Laboratories at The Institute of Cancer Research. It is the first dedicated breast cancer research facility in the UK and, under the directorship of Professor Alan Ashworth, its 100 scientists and clinicians are working on a programme of cutting edge biological research that ultimately aims to eradicate breast cancer, by discovering the causes of the disease, finding methods of prevention and developing new treatments and more effective diagnosis.

The Institute of Cancer Research:

* The Institute of Cancer Research is Europe's leading cancer research centre with expert scientists working on cutting edge research. It was founded in 1909 to carry out research into the causes of cancer and to develop new strategies for its prevention, diagnosis, treatment and care. Website at: http://www.icr.ac.uk.

* The Institute works in a unique partnership with The Royal Marsden NHS Foundation Trust, forming the largest comprehensive cancer centre in Europe. This relationship enables close daily contact with those on the frontline in the fight against cancer - the clinicians, the carers and most importantly, the patients.

Breast Cancer:

* Breast cancer is now the commonest cancer in UK women, accounting for nearly 1 in 3 of all female cancers.

* Over 44,000 women are diagnosed with breast cancer every year in the UK and 35 women will die every day from this disease.

* Breakthrough has developed a handbag-sized guide - Breast Cancer Risk Factors: The Facts - to help improve our understanding of the known causes of breast cancer.

http://www.breakthroughcentre.org.uk