Vattikuti Urology Institute, Henry Ford Health System, Detroit, MI 48202, USA.
Cancer Lett. 2013 Aug 9;336(1):185-95. doi: 10.1016/j.canlet.2013.04.027. Epub 2013 May 2.
Inhibition of 5-Lox induces apoptosis in prostate cancer cells by inactivating PKCε which is prevented by 5-oxoETE, and activators of PKCε prevent 5-Lox inhibition-induced apoptosis, suggesting that 5-Lox metabolites exert survival signaling via PKCε. However, mechanisms by which 5-Lox metabolites activate PKCε are not understood yet. We found that prostate cancer cells express high levels of OXER1, a G protein-coupled 5-oxoETE receptor, which delivers signal by generating diacyl-glycerol through phospholipase C-beta. Interestingly, we found that U73122, an inhibitor of PLC-beta, interrupts the apoptosis-preventing effect of 5-oxoETE, and exogenous diacyl-glycerol effectively prevents 5-Lox inhibition-induced apoptosis, suggesting that 5-oxoETE signals via OXER1 to promote prostate cancer cell survival.
5-LOX 的抑制通过使 PKCε 失活诱导前列腺癌细胞凋亡，而 5-oxoETE 可阻止这种失活，PKCε 的激活剂可防止 5-LOX 抑制诱导的细胞凋亡，这表明 5-LOX 代谢物通过 PKCε 发挥生存信号。然而，目前尚不清楚 5-LOX 代谢物激活 PKCε 的机制。我们发现前列腺癌细胞表达高水平的 OXER1，一种 G 蛋白偶联的 5-oxoETE 受体，它通过磷酸脂酶 C-β产生二酰基甘油传递信号。有趣的是，我们发现 U73122（PLC-β 的抑制剂）中断了 5-oxoETE 的抗凋亡作用，外源性二酰基甘油有效地防止了 5-LOX 抑制诱导的细胞凋亡，这表明 5-oxoETE 通过 OXER1 传递信号以促进前列腺癌细胞的存活。
