Scientists discover genetic 'off switch' for series of cancers

Published Date: 24 February 2009
By Shan Ross

SCIENTISTS have identified a cancer "master 
switch" that could open the door to revolutionary 
new treatments, research published today reveals.

Activating a specific gene common to fruit flies, 
mice and humans may allow cancer to be "switched off", researchers say.

The work has major implications for treating and 
curing cancers by snuffing out the root of tumour formation.

Last night, cancer charities welcomed the 
research into the disease, which is one of the top three killers in Scotland.

Each year, 289,000 people in the UK are diagnosed 
with cancer including 27,000 in Scotland – 74 a day.

The discovery outlined in two scientific papers 
today relates to eye tumours in flies and bowel 
cancers in mice and humans. But other "master 
switches" common to different species may exist for other cancers.

All belong to a gene family vital to 
"differentiation", the process by which cells 
acquire specialist roles in the body.

Cancer cells, by definition, have no function and 
are less differentiated than normal cells.

The new research, published in the online journal 
PLoS Biology, focuses on the Atoh1 gene in mice 
and humans and its fruit fly equivalent, Ato. 
Both belong to the "Atonal" group of genes, which 
are thought to be key controllers.

Scientists showed that Atoh1 suppressed bowel 
cancer in both mice and humans, while Ato 
prevented eye tumours developing in fruit flies.

Switching off the gene triggered the growth of 
cancers in flies, mice and humans. Mice lacking 
Atoh1 developed bowel cancer. The same was true with human patients.

Laboratory experiments showed that loss of Atoh1 
not only led to the formation and growth of bowel 
cancer, but also Merkel cell carcinoma – a rare but deadly form of skin cancer.

Reactivating the gene in laboratory-grown cancer 
cells caused the tumours to stop dividing and die.

Separate teams of scientists led by Dr Wouter 
Bossuyt, of the VIB biotechnology institute and 
KU Leuven School of Medicine in Belgium, carried out the research.

The authors wrote: "We suggest that Ato/Atoh1 and 
similar genes are important brakes on malignant transformation."

Cells begin differentiating in the womb. During 
embryonic development, they repeatedly divide and 
become increasingly different from each other.

In an adult, almost every cell is highly 
specialised and assigned a particular job. Skin, 
liver, nerve and bone cells all look and behave differently.

Cancer reverses the process, causing cells to 
become less differentiated. Like the cells of the 
developing embryo, cancer cells also divide rapidly.

Atoh1 appears to switch on the last step in the 
specialisation of cells lining the intestine. 
Removing or deactivating it reverses 
differentiation, leading to cancer. Reactivating 
it engages the differentiation process again and suppresses tumour formation.

Dr Bossuyt and his colleagues raised the 
possibility of further "master switch" genes affecting other cancers.

There was already evidence that related genes 
might play a role in the early stages of breast 
cancer development, the scientists said.

Dr Joanna Owens, Cancer Research UK's science 
information manager, said: "This is an exciting 
addition to what we already know about the key 
molecular triggers for cancer formation. If we 
can understand more about these crucial events, 
we can find new ways to put the brakes on cancer."

A spokesman for Macmillan Cancer Support in 
Scotland said: "Early diagnosis and treatment of 
cancer is essential for improving survival rates 
and reducing anxiety and distress in patients, so 
news about any new potential treatment is always welcome.

"However, with two million people now living with 
or beyond cancer in the UK, support and access to information is also crucial."

<http://news.scotsman.com/health/Scientists-discover--genetic-.5008365.jp>http://news.scotsman.com/health/Scientists-discover--genetic-.5008365.jp
 


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