Antiapoptotic signaling in LNCaP prostate cancer cells: a survival signaling pathway independent of phosphatidylinositol 3'-kinase and Akt/protein kinase B.
Antiapoptotic signaling in LNCaP prostate cancer cells: a survival signaling pathway independent of phosphatidylinositol 3'-kinase and Akt/protein kinase B.
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发表时间：
1999-04
期刊：
影响因子：
11.2
通讯作者：
Jonathan P. Carson;G. Kulik;Michael J. Weber
中科院分区：
文献类型：
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作者：
Jonathan P. Carson;G. Kulik;Michael J. Weber
磷脂酰肌醇3 '-激酶（PI 3激酶）-Akt/蛋白激酶B（PK B）“存活信号传导”途径的组成性激活是许多癌症变得对细胞毒性疗法难治的可能机制。在LNCaP前列腺癌细胞中，PTEN磷酸肌醇磷酸酶失活，导致Akt/PKB的组成性激活和对细胞凋亡的抗性。然而，凋亡和Akt/PKB的失活可以诱导这些细胞与PI 3激酶抑制剂的治疗。令人惊讶的是，雄激素，表皮生长因子，或血清可以保护这些细胞免于凋亡，即使在PI 3激酶抑制剂的存在下，没有Akt/PKB的激活，表明一种新的，Akt/PKB独立的生存途径的活性。该途径在半胱天冬酶3激活和细胞色素c从线粒体释放之前的水平阻断细胞凋亡。
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.