ABSTRACT: Phosphatidylinositol 3-kinase (PI3K) signalling plays a pivotal role in intracellular signal transduction pathways involved in cell growth, cellular transformation, and tumourigenesis. PI3K is overexpressed in many human cancers, including endometrial carcinomas, one of the most common female genital tract malignancies. Here, we used small interfering RNA (siRNA) targeted to PI3K p110-beta to determine whether inhibition of the beta isoform could be a potential therapeutic target for endometrial carcinoma. In this study, treatment of HEC-1B endometrial cancer cells with PI3K p110-beta-specific siRNA resulted in increased apoptosis and decreased tumour cell proliferation. Depletion of PI3K p110-beta decreased the protein levels of AKT1, AKT2, pAKT, and mTOR-downstream targets of PI3K. Knock-down of PI3K p110-beta by siRNA also induced decreased expression of cyclin E and Bcl-2, suggesting that PI3K p110-beta stimulates tumour growth, at least in part by regulating cyclin E and Bcl-2. Thus, our results indicate that siRNA-mediated gene silencing of PI3K p110-beta may be a useful therapeutic strategy for endometrial cancers overexpressing PI3K p110-beta.
The Journal of Pathology 06/2007; 212(2):161-9. · 6.32 Impact Factor