http://news.bbc.co.uk/2/hi/health/4861500.stm
Mutant gene's kidney cancer clue
Scientists have discovered how a faulty gene can increase the risk of kidney tumours.
Imperial College London researchers looked at cells from people with VHL syndrome - an inherited condition.
They found the cells behave as if they have too little oxygen - setting off a chain of events which can lead to them becoming cancerous.
Experts said the discovery, detailed in Cancer Research, could pave the way for new treatments.
Over 6,600 people are diagnosed with kidney cancer each year in the UK, with almost two-thirds over 65-years-old.
The researchers looked at people with von Hippel-Lindau (VHL) syndrome which increases a person's risk of developing benign and malignant tumours in the kidneys - as well as of rare forms of tumours in other parts of the body -because of faults in the VHL gene.
The gene normally safeguards cells against cancer.
People in families with a faulty VHL gene have a 50% chance of inheriting the faulty gene - and if they do they then have a 70% chance of developing kidney cancer at some point in their lives.
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Lack of oxygen
Until now, it has not been clear how faults in VHL can lead to the development of kidney cancer
But the researchers found that kidney cells with faulty VHL were lacking a normal protein molecule, called e-cadherin, which contributes to normal cell behaviour.
They found that the cells behaved as if they were receiving much less oxygen than they really were.
To combat this perceived lack of oxygen, the cells raised a chemical signal called HIF (hypoxia-inducible factor).
HIF causes the kidney cells to switch off e-cadherin.
Normally, the e-cadherin protein molecule plays an important role in helping cells to stick together to form healthy tissues.
The loss of this molecule results in a breakdown in communication between neighbouring cells.
Cells then acquire important features of cancer, such as invasion and spread.
The scientists say their finding could also have implications for other types of cancer, as low oxygen levels are common in tumours.
E-cadherin is also lost in several forms of cancer, including breast cancer.
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Mechanism
Professor Patrick Maxwell, who led the research, said: "It is very powerful scientifically to be able to study cells before they become cancerous, as it helps us to understand how tumours develop.
"Kidney cancer is usually detected late meaning the only form of treatment is radical surgery.
"Investigating cells before they develop into tumours could help us to find a way to detect and treat kidney cancer earlier."
But he added: "We don't think loss of e-cadherin is the only thing responsible for the development of kidney cancer.
"In fact there are probably many more factors involved, and our next task is to find out what these are, and work out the best way to prevent this disease from forming in the first place."
Professor John Toy, Medical Director of Cancer Research UK, said: "By examining the relationship between oxygen levels and e-cadherin, the research group has discovered a potential mechanism by which mutant VHL could contribute to tumour development.
"This is extremely interesting research as it could pave the way for new treatments and offer hope to patients with VHL syndrome."
The work was funded by Cancer Research UK, the Medical Research Council and the Wellcome Trust.
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http://news.bbc.co.uk/2/hi/health/4861500.stm
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