‘Mutant’ gene offers new clue to kidney cancer

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.”

ENDS

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