Pim-1 knockdown potentiates paclitaxel-induced apoptosis in human hormone-refractory prostate cancers through inhibition of NHEJ DNA repair
Journal
Cancer Letters
Journal Volume
319
Journal Issue
2
Pages
214-222
Date Issued
2012
Author(s)
Abstract
The knockdown of Pim-1 or inhibition of Pim-1 activity significantly increased γ-H2A.X expression. The effect was correlated to apoptosis and was attributed to the inhibition of nonhomologous DNA-end-joining (NHEJ) repair activity supported by the following observations: (1) inhibition of ATM and DNA-PKcs activities, (2) down-regulation of Ku expression and nuclear localization and (3) decrease of DNA end-binding of both Ku70 and Ku80. The data suggest that Pim-1 plays a crucial role in the regulation of NHEJ repair. In the absence of Pim-1, the ability of DNA repair significantly decreases when exposed to paclitaxel, leading to severe DNA damage and apoptosis. ? 2012 Elsevier Ireland Ltd.
SDGs
Other Subjects
ATM protein; histone H2AX; Ku antigen; Ku80 antigen; paclitaxel; protein kinase Pim 1; small interfering RNA; unclassified drug; apoptosis; article; cell nucleus; controlled study; correlation analysis; DNA end joining repair; down regulation; gene silencing; human; human cell; male; priority journal; prostate cancer; protein expression; protein function; protein localization; Apoptosis; Cell Line, Tumor; Cell Proliferation; DNA End-Joining Repair; DNA Helicases; DNA-Binding Proteins; Drug Resistance, Neoplasm; Gene Knockdown Techniques; Histones; Humans; Male; Microtubules; Paclitaxel; Prostatic Neoplasms; Proto-Oncogene Proteins c-pim-1
Type
journal article