McEleny Kevin R, Watson R William G, Coffey Ronan N T, O'Neill Amanda J, Fitzpatrick John M
Department of Surgery, Mater Misericordiae Hospital, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, 47 Eccles Street, Dublin 7, Ireland.
Prostate. 2002 May 1;51(2):133-40. doi: 10.1002/pros.10061.
The caspases are the central executioners of apoptosis. The inhibitors of apoptosis proteins (IAPs) are a family of recently described caspase inhibitors. We hypothesised that tumor resistance to apoptosis could be due in part to IAP expression.
The expression of NAIP, cIAP-1, cIAP-2, XIAP, and survivin was investigated in the prostate cancer cell lines LNCaP, PC3, and DU145. RNase protection assays and Western blotting were used to assess RNA and protein expression. Apoptotic susceptibility was determined using etoposide and assessed by propidium iodide (PI) DNA incorporation using flow cytometry.
DU145 and PC3 cells were more resistant to apoptosis than LNCaP cells. All the IAPs were identified in the cell lines with variation in IAP expression between different cell types. Immunohistochemistry demonstrated cIAP-1 expression in PC3 cells was nuclear, while the expression of cIAP-2 and XIAP was perinuclear. Growing LNCaP cells in charcoal-stripped or androgen-supplemented medium resulted in no alteration in IAP expression.
This study characterises the expression of IAP in three of the most commonly used prostate cancer cells. IAP may make an important contribution to apoptotic resistance in patients with prostate cancer.
半胱天冬酶是细胞凋亡的核心执行者。凋亡抑制蛋白（IAPs）是最近发现的一类半胱天冬酶抑制剂。我们推测肿瘤对凋亡的抗性可能部分归因于IAP的表达。
研究了前列腺癌细胞系LNCaP、PC3和DU145中NAIP、cIAP-1、cIAP-2、XIAP和生存素的表达。采用核糖核酸酶保护试验和蛋白质印迹法评估RNA和蛋白质表达。使用依托泊苷测定凋亡敏感性，并通过流式细胞术检测碘化丙啶（PI）掺入DNA的情况进行评估。
DU145和PC3细胞比LNCaP细胞对凋亡更具抗性。在所有细胞系中均鉴定出所有IAP，不同细胞类型之间IAP表达存在差异。免疫组织化学显示，PC3细胞中cIAP-1的表达位于细胞核，而cIAP-2和XIAP的表达位于细胞核周围。在去除活性炭或添加雄激素的培养基中培养LNCaP细胞，IAP表达无变化。
本研究对三种最常用的前列腺癌细胞中IAP的表达进行了表征。IAP可能在前列腺癌患者的凋亡抗性中起重要作用。
