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Scientists discover a molecular 'switch' in cancers of the testis and ovary
Date:7/31/2013

Cambridge scientists have identified an 'on/off' switch in a type of cancer which typically occurs in the testes and ovaries called 'malignant germ cell tumours'. The research was published today, 01 August, in the journal Cancer Research.

Malignant germ cell tumours arise in sperm- or egg-forming cells and usually occur in the reproductive organs, the testes or ovaries. The cancerous tumours are seen in patients of all ages, both in childhood and adulthood.

Although many patients do well after treatment, current chemotherapy treatments can have severe long-term side effects, including hearing loss and damage to the kidneys, lungs and bone marrow. For some patients, outcomes remain poor and testicular cancer continues to be a leading cause of death in young men.

The scientists found that all malignant germ cell tumours contain large amounts of a protein called LIN28. This results in too little of a family of tiny regulator molecules called let-7. In turn, low levels of let-7 cause too much of numerous cancer-promoting proteins in cells. Importantly, the cancer-promoting proteins include LIN28 itself, so there is a vicious cycle that acts as an 'on' switch to promote malignancy. The researchers have likened these changes to a 'cascade effect', extending down from the large amounts of LIN28 to affect many properties of the cancer cells.

The researchers also discovered that by reducing amounts of the protein LIN28, or by directly increasing amounts of let-7, it is possible to reverse the vicious cycle. Both ways reduced levels of the cancer-promoting proteins and inhibited cell growth. Because the level of LIN28 itself goes down, the effects are reinforced and act as an 'off' switch to reduce cancerous behaviour.

Prof Nick Coleman, Professor of Molecular Pathology, Cambridge University said: "We need new ways of treating patients with malignant germ cell tumours, to minimise the toxic effects of chemotherapy and
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Contact: Genevieve Maul
gm349@admin.cam.ac.uk
44-012-237-65542
University of Cambridge
Source:Eurekalert

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