Department of Orthopaedic Surgery, Kurume University School of Medicine, Kurume 830-0011, Japan.
Oncol Rep. 2010 Sep;24(3):721-5. doi: 10.3892/or_00000913.
The N-myc downstream regulated gene 1 (NDRG1)/Cap43 is closely associated with cell differentiation, and its expression is induced by hypoxia and increasing intracellular calcium levels. Whether the NDRG1/Cap43 expression in cancer cells is a predictive marker of good or poor prognosis in patients, depends upon tumor types and differentiation status. In this study, we examined whether the NDRG1/Cap43 expression was involved in the differentiation of osteosarcoma cells, using three osteosarcoma cell lines, MG63, U2OS and SaOS2. The NDRG1/Cap43 expression in MG63 and U2OS was significantly enhanced by vitamin D3, which also induced the production of osteocalcin, a differentiation marker of osteoblasts. The knockdown of NDRG1/Cap43 using small interfering RNA also suppressed the production of osteocalcin and enhanced cell proliferation, accompanied by the suppression of p21 expression. Furthermore, the acquired invasiveness of osteosarcoma cells during the invasion in Matrigel resulted in the decreased expression of NDRG1/Cap43. On the basis of these results, our proposed role for NDRG1/Cap43 would be in the capacity of differentiation and invasion in osteosarcoma cells.
N- 神经母细胞瘤下调基因 1（NDRG1）/Cap43 与细胞分化密切相关，其表达受缺氧和细胞内钙离子水平升高的诱导。NDRG1/Cap43 在癌细胞中的表达是否是患者预后良好或不良的预测标志物，取决于肿瘤类型和分化状态。在这项研究中，我们使用三种骨肉瘤细胞系 MG63、U2OS 和 SaOS2 研究了 NDRG1/Cap43 的表达是否参与骨肉瘤细胞的分化。维生素 D3 显著增强了 MG63 和 U2OS 中的 NDRG1/Cap43 表达，同时还诱导了成骨细胞分化标志物骨钙素的产生。使用小干扰 RNA 敲低 NDRG1/Cap43 也抑制了骨钙素的产生并增强了细胞增殖，同时抑制了 p21 的表达。此外，骨肉瘤细胞在 Matrigel 中的侵袭过程中获得的侵袭性导致 NDRG1/Cap43 的表达降低。基于这些结果，我们提出 NDRG1/Cap43 的作用可能是在骨肉瘤细胞的分化和侵袭能力中发挥作用。
