Menschikowski Mario, Hagelgans Albert, Gussakovsky Eugene, Kostka Heike, Paley Elena L, Siegert Gabriele
Technische Universität Dresden, Medizinische Fakultät Carl Gustav Carus, Institut für Klinische Chemie und Laboratoriumsmedizin, Dresden, Germany.
Neoplasia. 2008 Mar;10(3):279-86. doi: 10.1593/neo.07965.
Upregulation of group IIA phospholipase A(2) (sPLA(2)-IIA) correlates with prostate tumor progression suggesting prooncogenic properties of this protein. Here, we report data on expression of three different sPLA(2) isozymes (groups IIA, V, and X) in normal (PrEC) and malignant (DU-145, PC-3, and LNCaP) human prostate cell lines. All studied cell lines constitutively expressed sPLA(2)-X, whereas sPLA(2)-V transcripts were identified only in malignant cells. In contrast, no expression of sPLA(2)-IIA was found in PrEC and DU-145 cells, but it was constitutively expressed by IFN-gamma in LNCaP and PC-3 cells. Expression of sPLA(2)-IIA is upregulated in PC-3 and in PrEC cell in a signal transducer and activator of transcription-1-dependent manner, but not in LNCaP cell. Additional signaling pathways regulating sPLA(2)-IIA expression include cAMP/protein kinase A, p38 mitogen-activated protein kinase, protein kinase C, Rho-kinase, and mitogen-activated/extracellular response protein kinase / extracellular signal-regulated kinase. No deletions were revealed in the sPLA(2)-IIA gene from DU-145 cells lacking the expression of sPLA(2)-IIA. Reexpression of sPLA(2)-IIA was induced by 5-aza-2'-deoxycytidine demonstrating that DNA methylation is implicated in the regulation of sPLA(2)-II. Together, these data suggest that sPLA(2)-IIA and sPLA(2)-V, but not sPLA(2)-X, are differentially expressed in normal and malignant prostate cells under the control of proinflammatory cytokines; epigenetic mechanisms appear involved in the regulation of sPLA(2)-IIA expression, at least in DU-145 cells.
IIA 组磷脂酶 A2（sPLA(2)-IIA）的上调与前列腺肿瘤进展相关，提示该蛋白具有促癌特性。在此，我们报告了三种不同的 sPLA(2) 同工酶（IIA、V 和 X 组）在正常（PrEC）和恶性（DU-145、PC-3 和 LNCaP）人前列腺细胞系中的表达数据。所有研究的细胞系均组成性表达 sPLA(2)-X，而 sPLA(2)-V 转录本仅在恶性细胞中被鉴定到。相比之下，在 PrEC 和 DU-145 细胞中未发现 sPLA(2)-IIA 的表达，但在 LNCaP 和 PC-3 细胞中它由 IFN-γ 组成性表达。sPLA(2)-IIA 在 PC-3 和 PrEC 细胞中的表达以信号转导和转录激活因子 1 依赖的方式上调，但在 LNCaP 细胞中未上调。调节 sPLA(2)-IIA 表达的其他信号通路包括 cAMP/蛋白激酶 A、p38 丝裂原活化蛋白激酶、蛋白激酶 C、Rho 激酶以及丝裂原活化/细胞外反应蛋白激酶/细胞外信号调节激酶。在缺乏 sPLA(2)-IIA 表达的 DU-145 细胞的 sPLA(2)-IIA 基因中未发现缺失。5-氮杂-2'-脱氧胞苷诱导了 sPLA(2)-IIA 的重新表达，表明 DNA 甲基化参与了 sPLA(2)-II 的调节。总之，这些数据表明，在促炎细胞因子的控制下，sPLA(2)-IIA 和 sPLA(2)-V，而非 sPLA(2)-X，在正常和恶性前列腺细胞中差异表达；表观遗传机制似乎参与了 sPLA(2)-IIA 表达的调节，至少在 DU-145 细胞中是这样。
