An important discovery about how a faulty gene leads to kidney cancer could pave the way for new treatments to block kidney cancer growth, a study published today* (Monday 4 April 2006) reveals.

The Cancer Research UK funded group, also supported by the Medical Research Council and the Wellcome Trust, looked at samples of kidney cells from people with von Hippel-Lindau (VHL) syndrome. This inherited condition increases a person’s risk of a number of benign and malignant tumours – especially in the kidneys – due to faults in the VHL gene.

Until now, it has not been clear how faults in VHL can lead to the development of kidney cancer. But these findings shed light on how the faulty gene predisposes a cell to cancerous changes.

The researchers found that kidney cells with faulty VHL were lacking a normal protein molecule, called e-cadherin, which contributes to normal cell behaviour. By investigating the cells further, the team were able to discover the underlying mechanism behind this loss.

They found 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, e-cadherin plays an important role in helping cells to stick together to form healthy tissues. But the loss of this molecule results in a breakdown in communication between neighbouring cells. When this happens, cells acquire important features of cancer, such as invasion and spread.

This research 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.

Lead researcher, Professor Patrick Maxwell of Imperial College London, 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.”

“However, 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.”


For media enquiries please contact Emma Gilgunn-Jones on 020 7061 8311 or, out-of-hours, the duty press officer on 07050 264 059.


Case study of a brother and sister with VHL syndrome available for interview – contact the press office for more information.

*Regulation of E-cadherin expression by VHL and hypoxia-inducible factor (HIF). Cancer Research. Miguel A Esteban, Maxine G B Tran, Sarah K Harten, Peter Hill, Ashish Chandra, Raju Raval, Tim S O‘Brien, Patrick H Maxwell.

The work was funded by Cancer Research UK, the Medical Research Council and the Wellcome Trust.

Kidney cancer and von Hippel-Lindau syndrome

Over 6,600 people are diagnosed with kidney cancer each year in the UK. Nearly two out of three of them (62 per cent) are over 65 years old. Kidney cancer is rare in people under 50, it affects many more men than women and accounts for just over two percent of all new cancers diagnosed in the UK.

VHL syndrome is an inherited cancer syndrome and faults in the VHL gene run through affected families. Those that carry the faulty gene have VHL syndrome which gives them an increased risk of developing kidney cancer and several quite rare benign and malignant tumours in the brain, spine, pancreas, adrenal glands, eyes and inner ear.

The VHL gene normally safeguards cells against cancer. People in families with a faulty VHL gene have a 50 per cent chance of inheriting the faulty gene – and if they do they then have a 70 per cent chance of developing kidney cancer at some point in their lives.

Randomly occurring changes in the VHL gene are also involved in most people who develop kidney cancer without anyone else in the family being affected. Sporadic VHL mutations occur in most cases of clear cell renal cell cancer (CCRCC) – the most common type of kidney cancer in adults. Over 80 out of every 100 kidney cancers diagnosed in the UK are this type.

Screening is available if one of the inherited syndromes that increases the risk of kidney cancer runs in a family. This means having an ultrasound or MRI scan of the kidneys every year. There is also a genetic blood test for VHL syndrome. Further genetic tests may become available in the future.

Cancer Research UK’s patient information website CancerHelp UK ( provides clear, easy to understand information about cancer and treatments.

Cancer Research UK

  • Together with its partners and supporters, Cancer Research UK’s vision is to beat cancer.
  • Cancer Research UK carries out world-class research to improve understanding of the disease and find out how to prevent, diagnose and treat different kinds of cancer.
  • Cancer Research UK ensures that its findings are used to improve the lives of all cancer patients.
  • Cancer Research UK helps people to understand cancer, the progress that is being made and the choices each person can make.
  • Cancer Research UK works in partnership with others to achieve the greatest impact in the global fight against cancer.
  • For further information about Cancer Research UK’s work or to find out how to support the charity, please call 020 7009 8820 or visit

Medical Research Council

  • The Medical Research Council (MRC) is a national organisation funded by the UK tax-payer. Its business is medical research aimed at improving human health; everyone stands to benefit from the outputs. The research it supports and the scientists it trains meet the needs of the health services, the pharmaceutical and other health-related industries and the academic world.
  • MRC has funded work which has led to some of the most significant discoveries and achievements in medicine in the UK.
  • About half of the MRC’s expenditure of £510 million is invested in its 40 Institutes, Units and Centres. The remaining half goes in the form of grant support and training awards to individuals and teams in universities and medical schools.
  • For further information, contact the Press Office on 0207 637 6011 or visit

Imperial College London

Consistently rated in the top three UK university institutions, Imperial College London is a world leading science-based university whose reputation for excellence in teaching and research attracts students (11,000) and staff (6,000) of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and management and delivers practical solutions that enhance the quality of life and the environment – underpinned by a dynamic enterprise culture. Website:

The Welcome Trust

The Wellcome Trust is the most diverse biomedical research charity in the world, spending about £450 million every year both in the UK and internationally to support and promote research that will improve the health of humans and animals.

The Trust was established under the will of Sir Henry Wellcome, and is funded from a private endowment, which is managed with long-term stability and growth in mind.