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Abstract: Human NDRG2 (N-Myc downstream regulated gene 2) was identified as a candidate tumor suppressor gene due to its low expression in human glioma and other cancer tissues. However, the mechanisms that lead to inactivation of the NDRG2 gene remain unknown. In the present study, semi-quantitative RT-PCR and Western blot analysis were used to confirm that NDRG2 mRNA and protein levels are decreased in several cancer cell lines. We found heterozygous deletion of NDRG2 in MCF-7 cells, and showed that mutation (at −13bp (C>T)) and methylation of the NDRG2 promoter occurred in several cancer cell lines. Furthermore, mutation (−13bp (C>T)) of the NDRG2 core promoter significantly reduced NDRG2 activity. Finally, we showed that NDRG2 expression was decreased in several breast cancer tissues. Unexpectedly, changes in the NDRG2 gene were not observed. Here, we describe for the first time, the mechanisms involved in NDRG2 gene down-regulation. [Copyright &y& Elsevier]

Abstract: NDRG2, a member of N-Myc downstream regulated gene family, exerts the important functions in cell differentiation and tumor suppression. Although the ectopic expressed Ndrg2 inhibits the proliferation of tumor cells, its intracellular signal transduction pathway is hardly known. Here, we identified MSP58, a 58-kDa microspherule protein, as an interacting partner of human Ndrg2 by using yeast two-hybrid screening. The interaction was confirmed by glutathione S-transferase pull-down assay in vitro and by co-immune-precipitation assay in vivo. The forkhead associated domain of MSP58 is essential for its interaction with Ndrg2. Ndrg2 could co-localize with MSP58 in nuclear of HeLa cell during cell stress. Furthermore, the modulation of Ndrg2 level influences the cell cycle process together with MSP58. In conclusion, the findings offered a novel insight into the physiological roles of Ndrg2. [Copyright &y& Elsevier]