The cAMP phosphodiesterase-4D7 (PDE4D7) is downregulated in androgen-independent prostate cancer cells and mediates proliferation by compartmentalising cAMP at the plasma membrane of VCaP prostate cancer cells

摘要: Isoforms of the PDE4 family cAMP-specific phosphodiesterases (PDEs) are expressed in a cell type-dependent manner and contribute to underpinning paradigm intracellular cAMP signal compartmentalisation. Here we identify differential regulation PDE4D7 isoform during prostate cancer progression uncover role controlling proliferation.  transcripts from 19 lines xenografts were quantified by qPCR. expression was further investigated because its significant downregulation between androgen-sensitive (AS) androgen-insensitive (AI) samples. Western blot analysis, PDE activity assay, immunofluorescent staining responsive FRET assays used investigate sub-plasma membrane localisation population VCaP PC3 lines. Disruption this pattern using dominant-negative protein siRNA knockdown showed that acts opposition proliferative signalling as assessed electrical impedance-based proliferation assays.  progression. is highly AS cells starkly downregulated AI The significance underscored our finding contributes major fraction degrading tethered at plasma displacement compartment leads an increase cells. mRNA not, however, directly regulated androgen receptor axis despite overlapping genomic structure with gene PART1. PDE4D7, which locates membrane, supress aberrant non-steroidal growth signals within or metastasis.  significantly phenotypes. This change potentially provides novel androgen-independent biomarker manipulation may provide therapeutic possibilities insights into contributory aspects complex molecular pathology cancer.