Overexpression of NDRG2 Can Inhibit Neuroblastoma Cell Proliferation through Negative Regulation by CYR61

Zhi-Guo Zhang,Lin Wu,Guo-Dong Gao,Jian Zhang,Jing Zhang,Gang Li,Huai-Zhou Qin,Da-Yun Feng,Lian-Ting Ma

doi:10.7314/apjcp.2014.15.1.239

Abstract

Several recent studies have showed that the n-myc downstream regulated gene 2 (NDRG2) is a new tumor suppressor gene, and that it plays an important role in tumor suppression in several cancers or cancer cell lines. However, few studies focused on its function in neuroblastoma cells. In the present investigation, we demonstrated that NDRG2 overexpression inhibited their proliferation. Using a cDNA microarray, we found that overexpression of NDRG2 inhibited the expression of cysteine-rich protein 61 (CYR61), a proliferation related gene. From our research, CYR61 may partially hinder NDRG2-mediated inhibition of cell proliferation. Overexpression of NDRG2 resulted in accumulation of cells in the G1 phase, which was accompanied by upregulation of p21 and p27 and downregulation of CDK4 and cyclin D1. Taken together, these data indicate that NDRG2 inhibits the proliferation of neuroblastoma cells partially through suppression of CYR61. Our findings offer novel insights into the physiological roles of NDRG2 in neuroblastoma cell proliferation, and NDRG2 may prove to be effective candidate for the treatment of children with neuroblastoma.

Highlights

Neuroblastoma (NB) is one of the most common solid tumors in childhood, and is remarkable due to its broad spectrum of clinical behavior
Several recent studies have showed that the n-myc downstream regulated gene 2 (NDRG2) is a new tumor suppressor gene, and that it plays an important role in tumor suppression in several cancers or cancer cell lines
To explore whether cysteine-rich protein 61 (CYR61) participates in NDRG2mediated inhibition of cell proliferation, we introduced CYR61 into two NB cell lines by pcDNA3.1-CYR61 vector; expression was confirmed by Western blot (Figure 4A)

Summary

Introduction

Neuroblastoma (NB) is one of the most common solid tumors in childhood, and is remarkable due to its broad spectrum of clinical behavior. NDRG2 was identified as a new tumor suppressor gene, and its expression was decreased or undetectable in various tumors and tumor cell lines when compared to the normal tissue or cell lines (Lorentzen et al, 2007; Ma et al, 2008; Zhao et al, 2008; Kim et al, 2009; Lorentzen et al, 2011). These findings suggested that NDRG2 participates in modulation of the malignant progression of tumors. Accumulation evidence suggests that NDRG2 plays a role as a tumor suppressor, but its exact functional role in cells remains to be clarified, especially in the unreported tissues or cell lines like NB

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Conclusion