Abstract 2287: Nuclear localization of N-myc downstream regulated gene 4: A novel therapeutic target in meningioma

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA NDRG4 is a member of the N-Myc downregulated gene family (NDRG) belonging to the alpha/beta hydrolase super family. The roles of NDRG4 in meningioma tumor development have not previously been evaluated. Effective local therapies include surgery and radiation, but there is a need for novel molecular targets to improve survival and reduce morbidity for meningioma patients. We have recently identified the N-Myc down regulated gene 4, NDRG4, protein as being overexpressed in aggressive meningiomas and demonstrated that NDRG4 downregulation results in decreased cell viability, migration and invasive properties. NDRG4 was initially identified as a cytoplasmic protein. In the present study, we proposed that nuclear localization of NDRG4 and the role of NDRG4 in cell proliferation. Subcellular distribution of NDRG4 was identified by western blotting in nuclear and cytosolic extracts. Immunocytofluoresence analysis revealed the NDRG4 nuclear localization. Here we demonstrate that depletion of NDRG4 induces the predominant form of cell death is apoptosis, utilizing DNA laddering and Annexin V/APC flow cytometry assay. We show that apoptosis caused by transduction of lentiviral shNDRG4 involves of p53 phoshorylation at ser 15, Bax activation. Flow cytometry analysis revealed changes in mitochondrial membrane potential (Ψm), which was observed by JC-1. Sub-cellular distribution of Bax and Cytochrome c indicated the mitochondrial-mediated apoptosis. In conclusion, we show that NDRG4 is also a nuclear protein expressed in response to cell proliferation and demonstrated the suppression of NDRG4 induces the apoptosis through p53 and Bax mediated intrinsic apoptotic pathway. Citation Format: Rama P. Kotipatruni, Xuan Ren, Robert P. Vanderwaal, Dinesh Thotala, Jerry J. Jaboin. Nuclear localization of N-myc downstream regulated gene 4: A novel therapeutic target in meningioma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2287. doi:10.1158/1538-7445.AM2014-2287