Antiapoptotic signaling in LNCaP prostate cancer cells : A survival signaling pathway independent of phosphatidylinositol 3'-kinase and akt/protein kinase B

• Published in: Cancer research (Chicago, Ill.) Vol. 59; no. 7; pp. 1449 - 1453
• Main Authors: CARSON, J. P, KULIK, G, WEBER, M. J
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.04.1999
• Subjects: Apoptosis; Biological and medical sciences; Caspase 3; Caspases - metabolism; Culture Media, Serum-Free; Cytochrome c Group - physiology; Epidermal Growth Factor - pharmacology; Humans; Male; Medical sciences; Metribolone - pharmacology; Nephrology. Urinary tract diseases; Phosphatidylinositol 3-Kinases - physiology; Phosphorylation; Prostatic Neoplasms - pathology; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins - physiology; Proto-Oncogene Proteins c-akt; Tumor Cells, Cultured; Tumors of the urinary system; Urinary tract. Prostate gland; Human; Urinary system disease; Prostate disease; Enzyme; Transferases; Phosphoric monoester hydrolases; Esterases; Malignant tumor; In vitro; Signal transduction; Protein kinase; Established cell line; Hydrolases; Mechanism of action; Phosphatidylinositol-3-phosphatase; Male genital diseases; Prostate; Tumor cell; Apoptosis
• ISSN: 0008-5472; 1538-7445

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.