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  • Original Paper
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Alternative phospholipase D/mTOR survival signal in human breast cancer cells

Abstract

Cancer cells generate survival signals to suppress default apoptotic programs that protect from cancer. Phosphatidylinositol-3-kinase (PI3K) generates a survival signal that is frequently dysregulated in human cancers. Phospholipase D (PLD) has also been implicated in signals that promote survival. One of the targets of PLD signaling is mTOR (mammalian target of rapamycin), a critical regulator of cell cycle progression and cell growth. We report here that elevated PLD activity in the MDA-MB-231 human breast cancer cell line generates an mTOR-dependent survival signal that is independent of PI3K. In contrast, MDA-MB-435S breast cancer cells, which have very low levels of PLD activity, are dependent on PI3K for survival signals. The data presented here identify an alternative survival signal that is dependent on PLD and mTOR and is active in a breast cancer cell line where the PI3K survival pathway is not active.

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Acknowledgements

We thank Michael Frohman (SUNY, Stony Brook) for the mPLD2 genes used in this study and Bob Abraham (Burnham Institute) for the mTOR constructs. John Blenis is acknowledged for several helpful discussions. This work was supported by grants from the National Cancer Institute (CA46677) and a SCORE grant from the National Institutes of Health (GM60654). Research Centers in Minority Institutions award RR-03037 from the National Center for Research Resources of the National Institutes of Health, which supports infrastructure and instrumentation in the Biological Sciences Department at Hunter College, is also acknowledged.

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Correspondence to David A Foster.

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Chen, Y., Rodrik, V. & Foster, D. Alternative phospholipase D/mTOR survival signal in human breast cancer cells. Oncogene 24, 672–679 (2005). https://doi.org/10.1038/sj.onc.1208099

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