C72
Regulation of the class III PI 3-kinase, hVps34, in cancer cells
Krzysztofa Odrzywol, James T. Murray
Centre for Cancer Research and Cell Biology, Queen's University, Belfast, Northern Ireland, UK
Background
The class III phosphoinositide 3-kinase, hVps34 (PIK3C3), is a nutrient-sensitive lipid kinase that is required for mammalian target of rapamycin (mTOR) activation. The mammalian target of rapamycin (mTOR) pathway is required for regulating nutrient uptake, energy metabolism and cell proliferation and hyperactivating mutations in this pathway are commonly found in human cancers.
Results
Regulation of hVps34 in a cancer context has not previously been investigated; therefore we have profiled the expression and activity status of hVps34 in a panel of human cancer cell lines. We have screened ten cancer cell lines, including five breast and four colon carcinoma cell lines for differences in hVps34 expression and activity. We selected four of these cell lines for further analysis under nutrient and growth factor restricted conditions. When compared to expression and activity levels of mTOR and S6K1, we found that in MCF-7 cells, hVps34 protein expression inversely correlated with S6K1 expression and relative activity. MCF-7 cells have elevated levels of S6K1, due to a chromosomal amplification event. When MCF-7 cells challenged by chronic nutrient deprivation, S6K1 was inhibited, while hVps34 protein expression increased two-fold.
Conclusion
Our data suggest that differences in hVps34 expression between cancer cell lines exist, that hVps34 expression is influenced by the state of mTOR pathway activation and that this may have important implications for mTOR/S6K1 signalling in cancer cells.
