A newly identified genetic mutation found in several types of cancer makes cultured cells cancerous and induces leukaemia in mice. The find, reported in Nature, aids our basic understanding of cancer biology and may influence drug design and prescription.
AKT proteins have been implicated in many cellular processes including metabolism, programmed cell death and proliferation. But while AKT signalling has been implicated in cancer, activating point mutations have so far not been reported in human tumours. Studies by Kerry L. Blanchard and colleagues suggest a direct role of AKT1 mutations in human cancer.
The team identified a recurrent mutation in the AKT1 gene in biopsy samples from breast, colorectal and ovarian cancer. They then analysed the structure of the mutant protein, and found that it tends to be located near the cell's plasma membrane, where active AKT proteins are known to function. Critically, the mutation appears to activate the AKT protein, stimulating a cascade of downstream signals and making cultured cells cancerous. This mutant form of AKT1 also induced leukaemia in a mouse model.
Kerry L. Blanchard (Eli Lilly & Company, Indianapolis, IN, USA)
Abstract available online.
(C) Nature press release.
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