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Pim-1 knockdown potentiates paclitaxel-induced apoptosis in human hormone-refractory prostate cancers through inhibition of NHEJ DNA repair.

ABSTRACT: The knockdown of Pim-1 or inhibition of Pim-1 activity significantly increased ?-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.

SUBMITTER: Hsu JL

PROVIDER: S-EPMC4207118 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Pim-1 knockdown potentiates paclitaxel-induced apoptosis in human hormone-refractory prostate cancers through inhibition of NHEJ DNA repair.

Hsu Jui-Ling JL Leong Pui-Kei PK Ho Yunn-Fang YF Hsu Lih-Ching LC Lu Pin-Hsuan PH Chen Ching-Shih CS Guh Jih-Hwa JH

Cancer letters 20120117 2

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 regu ...[more]

PMID: 22261337

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