Nuclear Upregulation Of Class I Phosphoinositide 3-Kinase P110 Beta Correlates With High 47s Rrna Levels In Cancer Cells

The class I phosphoinositide 3-kinase (PI3K) catalytic subunits p110 alpha and p110 beta are ubiquitously expressed but differently targeted in tumours. In cancer, PIK3CB (encoding p110 beta) is seldom mutated compared with PIK3CA (encoding p110a) but can contribute to tumorigenesis in certain PTEN-deficient tumours. The underlying molecular mechanisms are, however, unclear. We have previously reported that p110 beta is highly expressed in endometrial cancer (EC) cell lines and at the mRNA level in primary patient tumours. Here, we show that p110 beta protein levels are high in both the cytoplasmic and nuclear compartments in ECcells. Moreover, high nuclear:cytoplasmic staining ratios were detected in high-grade primary tumours. High levels of phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5) P-3] were measured in the nucleus of EC cells, and pharmacological and genetic approaches showed that its production was partly dependent upon p110 beta activity. Using immunofluorescence staining, p110 beta and PtdIns(3,4,5)P-3 were localised in the nucleolus, which correlated with high levels of 47S pre-rRNA. p110 beta inhibition led to a decrease in both 47S rRNA levels and cell proliferation. In conclusion, these results present a nucleolar role for p110 beta that may contribute to tumorigenesis in EC.