Abstract
N-Myc downstream-regulated gene 2 (NDRG2) is a candidate tumor suppressor gene, which plays an important role in controlling tumor growth. The aim of this study was to investigate the expression of NDRG2 gene in bladder cancer (BC) tissues and several bladder cancer cell lines, and to seek its clinical and pathological significance. Ninety-seven bladder carcinoma and 15 normal bladder tissue sections were analyzed retrospectively with immunohistochemistry. The human bladder cancer cell line T24 was infected with LEN-NDRG2 or LEN-LacZ. The effects of NDRG2 overexpression on T24 cells and T24 nude mouse xenografts were measured via cell growth curves, tumor growth curves, flow cytometric analysis, western blot and Transwell assay. NDRG2 was highly expressed in normal bladder tissue, but absent or rarely expressed in cacinomatous tissues (χ2=8.761, p < 0.01). The NDRG2 level was negatively correlated with tumor grade and pathologic stage(r=-0.248, p < 0.05), as well as increased c-myc level (r=-0.454, p< 0.001). The expression of NDRG2 was low in the three BC cell lines. T24 cells infected with LEN-NDRG2 showed inhibition of proliferation both in vitro and in vivo, and NDRG2 overexpression can inhibit tumor growth and invasion in vitro.
Highlights
The incidence of bladder cancer is increasing
Immunohistochemistry showed that N-Myc downstream-regulated gene 2 (NDRG2) protein positive was staining in the cytoplasm of normal tissues and bladder carcinoma (Figure 1A)
NDRG2 is a candidate tumor suppressor gene, and a series of studies have confirmed that it plays an important role in cell proliferation, apoptosis and metastasis [15,16]
Summary
The incidence of bladder cancer is increasing. An estimated 386,300 new cases and 150,200 deaths from bladder cancer occurred in 2008 worldwide [1]. In more than 75% of the cases, the diagnosis is made at an early stage of disease (stages Ta and T1). Despite having received adequate treatment, the five-year overall survival rate for pathologic T2 disease is 52–77%, T3 disease 40–64%, and T4 or lymph node-positive disease 26–44% [3]. There are numeral therapeutic interventions to treat this disease; the overall survival rate has not been improved in the last twenty years. To establish a new mode of therapy using antioncogene agent to improve the survival rate of patients is highly desirable
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