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[Cancer Research 59, 1449-1453, April 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 1449-1453, April 1, 1999]
© 1999 American Association for Cancer Research

Advances in Brief

Antiapoptotic Signaling in LNCaP Prostate Cancer Cells

A Survival Signaling Pathway Independent of Phosphatidylinositol 3'-Kinase and Akt/Protein Kinase B1

Jonathan P. Carson, George Kulik and Michael J. Weber2

Department of Microbiology and Cancer Center, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908

Constitutive activation of the phosphatidylinositol 3'-kinase (PI3 kinase)-Akt/protein kinase B (PKB) "survival signaling" pathway is a likely mechanism by which many cancers become refractory to cytotoxic therapy. In LNCaP prostate cancer cells, the PTEN phosphoinositide phosphatase is inactivated, leading to constitutive activation of Akt/PKB and resistance to apoptosis. However, apoptosis and inactivation of Akt/PKB can be induced in these cells by treatment with PI3 kinase inhibitors. Surprisingly, androgen, epidermal growth factor, or serum can protect these cells from apoptosis, even in the presence of PI3 kinase inhibitors and without activation of Akt/PKB, indicating the activity of a novel, Akt/PKB-independent survival pathway. This pathway blocks apoptosis at a level prior to caspase 3 activation and release of cytochrome c from mitochondria.




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