脂筏微结构域的胆固醇水平通过表皮生长因子受体（EGFR）介导的Akt和细胞外信号调节激酶（ERK）信号转导来调控前列腺癌细胞的凋亡性细胞死亡。
Cholesterol level of lipid raft microdomains regulates apoptotic cell death in prostate cancer cells through EGFR-mediated Akt and ERK signal transduction.
作者信息
Oh Hea Young, Lee Eun Jin, Yoon Sun, Chung Byung Ha, Cho Kang Su, Hong Sung Joon
机构信息
Department of Urology, Urological Science Institute, Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Korea.
出版信息
Prostate. 2007 Jul 1;67(10):1061-9. doi: 10.1002/pros.20593.
BACKGROUND
Lipid rafts are cholesterol-enriched microdomains in cell membranes that have been shown to regulate signal transduction. We investigated whether membrane cholesterol could regulate apoptosis and attempted to elucidate the mechanism by which apoptosis is induced in prostate cancer cells.
METHODS
LNCaP cells were exposed to 2-hydroxyprophyl-beta-cyclodextrin (HPCD) to deplete membrane cholesterol. Cell viability and apoptosis were evaluated by Celltiter Bluetrade mark Cell Viability assay and ethidium bromide/acridine orange staining. Signal transduction was investigated by immunoblot analysis of cell lysates.
RESULTS
Cell viability was dose dependent inhibited by HPCD and restored by replenishment of cholesterol. HPCD induced apoptotic cell death through down-regulation of Bcl-xL and up-regulation of caspase-3 and PARP cleavages. HPCD inhibited both EGFR/Akt and EGFR/ERK signal transduction.
CONCLUSIONS
Lipid raft cholesterol regulates apoptotic cell death in prostate cancer cells through EGFR-mediated Akt and ERK pathways.
背景
脂筏是细胞膜中富含胆固醇的微结构域，已被证明可调节信号转导。我们研究了膜胆固醇是否能调节细胞凋亡，并试图阐明前列腺癌细胞中诱导细胞凋亡的机制。
方法
将LNCaP细胞暴露于2-羟丙基-β-环糊精（HPCD）以耗尽膜胆固醇。通过Celltiter Bluetrade mark细胞活力测定和溴化乙锭/吖啶橙染色评估细胞活力和凋亡。通过对细胞裂解物的免疫印迹分析研究信号转导。
结果
HPCD剂量依赖性地抑制细胞活力，并通过补充胆固醇得以恢复。HPCD通过下调Bcl-xL和上调caspase-3及PARP裂解诱导凋亡性细胞死亡。HPCD抑制EGFR/Akt和EGFR/ERK信号转导。
结论
脂筏胆固醇通过EGFR介导的Akt和ERK途径调节前列腺癌细胞的凋亡性细胞死亡。
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