Chen Yuhong, Rodrik Vanessa, Foster David A
Department of Biological Sciences, Hunter College of The City University of New York, New York, NY 10021, USA.
Oncogene. 2005 Jan 20;24(4):672-9. doi: 10.1038/sj.onc.1208099.
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.
癌细胞产生生存信号以抑制保护机体免受癌症侵害的默认凋亡程序。磷脂酰肌醇-3-激酶（PI3K）产生一种生存信号，该信号在人类癌症中经常失调。磷脂酶D（PLD）也与促进生存的信号有关。PLD信号的靶点之一是mTOR（雷帕霉素的哺乳动物靶点），它是细胞周期进程和细胞生长的关键调节因子。我们在此报告，MDA-MB-231人乳腺癌细胞系中升高的PLD活性产生一种不依赖PI3K的mTOR依赖性生存信号。相比之下，PLD活性非常低的MDA-MB-435S乳腺癌细胞依赖PI3K获取生存信号。此处呈现的数据确定了一种依赖PLD和mTOR的替代生存信号，该信号在PI3K生存途径不活跃的乳腺癌细胞系中具有活性。
