Differential Expression of Secretory Phospholipases A2 in Normal and Malignant Prostate Cell Lines: Regulation by Cytokines, Cell Signaling Pathways, and Epigenetic Mechanisms

Abstract

Upregulation of group IIA phospholipase A2 (sPLA2-IIA) correlates with prostate tumor progression suggesting prooncogenic properties of this protein. Here, we report data on expression of three different sPLA2 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 sPLA2-X, whereas sPLA2-V transcripts were identified only in malignant cells. In contrast, no expression of sPLA2-IIA was found in PrEC and DU-145 cells, but it was constitutively expressed by IFN-γ in LNCaP and PC-3 cells. Expression of sPLA2-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 sPLA2-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 sPLA2-IIA gene from DU-145 cells lacking the expression of sPLA2-IIA. Reexpression of sPLA2-IIA was induced by 5-aza-2′-deoxycytidine demonstrating that DNA methylation is implicated in the regulation of sPLA2-II. Together, these data suggest that sPLA2-IIA and sPLA2-V, but not sPLA2-X, are differentially expressed in normal and malignant prostate cells under the control of proinflammatory cytokines; epigenetic mechanisms appear involved in the regulation of sPLA2-IIA expression, at least in DU-145 cells.