The impact of altered annexin I protein levels on apoptosis and signal transduction pathways in prostate cancer cells
The impact of altered annexin I protein levels on apoptosis and signal transduction pathways in prostate cancer cells
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DOI：
10.1002/pros.20457
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发表时间：
2006-09-15
期刊：
影响因子：
2.8
通讯作者：
Ornstein, David K.
中科院分区：
文献类型：
--
作者：
Hsiang, Chin-Hui;Tunoda, Toshiyuki;Ornstein, David K.
背景尽管膜联蛋白I（ANX I）蛋白表达水平降低是前列腺癌所有阶段的共同发现，但ANX I失调与前列腺癌发展之间的因果关系尚未建立。在LNCaP和MDA PCa 2b中恢复了膜联蛋白I的表达，而LNCaP和MDA PCa 2b通常表达低水平或检测不到ANX I蛋白。检测恢复ANX I表达对细胞活力、软琼脂集落形成、细胞凋亡和细胞外信号调节激酶（ERK）、p38、c-Jun N-末端激酶（JNK）活化的影响。恢复ANXI表达除了诱导细胞凋亡外，还降低了细胞活力、集落形成。表皮生长因子的增殖反应通过恢复ANXI表达而被阻断。此外，在前列腺癌细胞中观察到ANX I表达恢复后磷酸化p38和JNK的基础和诱导水平增加。Annexin I可能在前列腺癌中具有肿瘤抑制功能。ANX I的促凋亡作用涉及p38和JNK的激活，这似乎使信号转导的平衡从增殖转向凋亡。
BACKGROUND. Although reduced expression levels of annexin I (ANX I) protein is a common finding in all stages of prostate cancer a causative relationship between ANX I dysregulation and prostate cancer development has yet to be established.METHODS. Annexin I expression was restored in LNCaP and MDA PCa 2b that normally express low or undetectable levels of ANX I protein. The impact of restoring ANX I expression on cell viability, colony formation in soft agar, apoptosis, and extracellular signal-regulated kinases (ERK), p38, c-Jun N-terminal kinases (JNK) activation was examined.RESULTS. Restoring ANX I expression reduced cell viability, colony formation, in addition to inducing apoptosis. The proliferative response of epidermal growth factor was blocked by restoring ANX I expression. Furthermore, increasing basal and induced levels of phosphorylated p38 and JNK were observed in prostate cancer cells following restoration of ANX I expression.CONCLUSIONS. Annexin I may have tumor suppressor functions in prostate cancer. The proapoptotic effect of ANX I involves the activation of p38 and JNK, which appears to shift the balance of signal transduction away from proliferation and toward apoptosis.