| dc.description.abstract | The PI3K pathway is highly dysregulated in human cancer. Class I PI3K phosphorylate the hydroxyl group of phosphatydilinositol (4,5)- biphosphate (PIP2) producing phosphatydilinositol (3,4,5)–triphosphate (PIP3), which recruits Akt to the membrane increasing cell growth, proliferation and survival. Gain-of-function mutations in class I PI3K genes are frequent in tumours. Although the highest mutation rates have been found for PIK3CA (p110α), other class I PI3K genes are also mutated in tumours. Saccharomyces cerevisiae lacks the orthologous class I PI3K and ectopic expression of hyperactive p110α variants induces toxicity, due to a decrease in essential PIP2 levels. The aim of this work has been to test the feasibility of a humanized S. cerevisiae model to analyse in vivo the activity of PIK3CB (p110β) tumourassociated mutations. PIK3CB mutations found in prostate, kidney and bladder tumour samples have been tested for toxicity in the yeast. Our results indicate that, in the tested conditions, the yeast S. cerevisiae system is not suitable to monitor the hyperactivity of the majority of PIK3CB tumour-associated mutations. We have found a PIK3CB mutation, T96A, which seems to inhibit growth in a yeast strain-dependent manner. This finding needs a more in depth verification and experimental confirmation. | es_ES |
