Background: Many lines of evidence suggest that poly(ADP-ribose) polymerase-1 (Parp-1) is involved in transcriptional regulation of various genes as a coactivator or a corepressor by modulating chromatin structure. However, the impact of Parp-1-deficiency on the regulation of genome-wide gene expression has not been fully studied yet. Results: We employed a microarray analysis covering 12,488 genes and ESTs using mouse Parp-1-deficient (Parp-1 ^-/-) embryonic stem (ES) cell lines and the livers of Parp-1 ^-/- mice and their wild-type (Parp-1 ^+/+) counterparts. Here, we demonstrate that of the 9,907 genes analyzed, in Parp-1 ^-/- ES cells, 9.6% showed altered gene expression. Of these, 6.3% and 3.3% of the genes were down- or up-regulated by 2-fold or greater, respectively, compared with Parp-1 ^+/+ ES cells (p < 0.05). In the livers of Parp-1 ^-/- mice, of the 12,353 genes that were analyzed, 2.0% or 1.3% were down- and up-regulated, respectively (p < 0.05). Notably, the number of down-regulated genes was higher in both ES cells and livers, than that of the up-regulated genes. The genes that showed altered expression in ES cells or in the livers are ascribed to various cellular processes, including metabolism, signal transduction, cell cycle control and transcription. We also observed expression of the genes involved in the pathway of extraembryonic tissue development is augmented in Parp-1 ^-/- ES cells, including H19. After withdrawal of leukemia inhibitory factor, expression of H19 as well as other trophoblast marker genes were further up-regulated in Parp-1 ^-/- ES cells compared to Parp-1 ^+/+ ES cells. Conclusion: These results suggest that Parp-1 is required to maintain transcriptional regulation of a wide variety of genes on a genome-wide scale. The gene expression profiles in Parp-1-deficient cells may be useful to delineate the functional role of Parp-1 in epigenetic regulation of the genomes involved in various biological phenomena.

Patients with metastatic castration-resistant prostate cancer (mCRPC) have poor outcomes. Docetaxel (DTX)-based therapy is a current standard treatment for patients with mCRPC. Approaches combining conventional chemotherapeutic agents and nanoparticles (NPs), particularly iron oxide NPs, may overcome the serious side effects and drug resistance, resulting in the establishment of new therapeutic strategies. We previously reported the combined effects of Fe₃O₄ nanoparticles (Fe₃O₄ NPs) with DTX on prostate cancer cells in vitro. In this study, we investigated the combined effects of Fe₃O₄ NPs and rapamycin or carboplatin on prostate cancer cells in vitro. Treatment of DU145 and PC-3 cells with Fe₃O₄ NPs increased intracellular reactive oxygen species (ROS) levels in a concentration-dependent manner. Treatment of both cell lines with 100 μg/mL Fe₃O₄ NPs for 72 h resulted in significant inhibition of cell viability with a different inhibitory effect. Combination treatments with 100 µg/mL Fe₃O₄ NPs and 10 µM carboplatin or 10 nM rapamycin in DU145 and PC-3 cells significantly decreased cell viability. Synergistic effects on apoptosis were observed in PC-3 cells treated with Fe₃O₄ NPs and rapamycin and in DU145 cells with Fe₃O₄ NPs and carboplatin. These results suggest the possibility of combination therapy with Fe₃O₄ NPs and various chemotherapeutic agents as a novel therapeutic strategy for patients with mCRPC.

Gene regulation during in vitro differentiation into adipocytes was examined in rat dental pulp–derived cells. Insulin, 3-isobutyl-1-methylxanthine, and dexamethasone were added to induce adipogenesis. Cells containing lipid droplets were observed after induction as in 3T3 L1 cells. Rat dental pulp–derived cells showed their potential to differentiate into adipocytes in vitro. In both types of cells, the pluripotent markers Oct-3/4 and Sox2 were downregulated during differentiation, whereas the expression of Nanog was not significantly changed during differentiation. Interestingly, in the dental pulp–derived cells, the level of Oct-3/4 was transiently induced at 1 week after induction and then significantly decreased during differentiation. Based on the expression profiles determined using GeneChip Arrays, 3418 probes across 10 clusters showed a difference in expression at 1, 2, and 3 weeks after induction versus before induction. Notably, genes in the PPAR signaling pathway including Pparγ, Fabp4, and the C/EBP family were upregulated by more than 3-fold. Upregulation of the PPAR pathways seems to be a critical signal transduction pathway in this differentiation system. These findings indicate that dental pulp–derived cells are a potential source of adipogenic cells, and their gene expression profile could be useful in future regenerative medicine applications.