Overexpression of N-Myc Downstream-Regulated Gene 2 (NDRG2) Regulates the Proliferation and Invasion of Bladder Cancer Cells In Vitro and In Vivo

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.

Growth differentiation factor-15: a p53- and demethylation-upregulating gene represses cell proliferation, invasion and tumorigenesis in bladder carcinoma cells

“…Although the function and expression of NDRG family genes with regard to bladder carcinoma cells remain poorly understood, our previous report has indicated that NDRG1 is upregulated by interleukin 6, which blocks cell proliferation and invasion in bladder carcinoma cells 27 . Further, a previous study found that NDRG2 expression is negatively correlated with pathologic stages, and NDRG2-overexpressed downregulates the proliferation and invasion of bladder carcinoma cells in vitro and in vivo 28 . Nowadays, no report has yet described the expression or regulation of NDRG3 in bladder cancer.…”

A 22q11.2 amplification in the region encoding microRNA-650 correlates with the epithelial to mesenchymal transition in breast cancer primary cultures of Mexican patients

“…On the other hand, siRNA-mediated knockdown of NDRG2 in MCF-7 cells resulted in increased COX-2 and NF-κB activity after PMA activation, correlating with an increased capacity of cell migration and invasion (51). There is also evidence that NDRG2 overexpression reduces proliferation, migration and invasion of lung, bladder, and colorectal cancer cells (28,52,53). …”

“…miR-650 is a novel oncomiR also implicated in EMT. miR-650 is often expressed in prostate, colorectal, hepatocellular, skin and gastric cancers (21–25), with evidence that it targets tumor suppressors ING4 and NDRG2 (23,26–28). ING4 and NDRG2 expression is often lost in cancer and different lines of evidence support their participation in EMT (29–33).…”

NDRG2 gene expression pattern in ovarian cancer and its specific roles in inhibiting cancer cell proliferation and suppressing cancer cell apoptosis

“…and cancer within neurotumors [15,16], gastroenteric tumors [9,17], genitourinary tumors [18,19], breast carcinoma [20,21], lung carcinoma [10,22], thyroid carcinoma [23], oral squamous-cell cancer [24], myeloid leukemia [25], and cervical cancer [14]. Collectively, the expression of NDRG2 is reduced within human tumors, while its overexpression suppresses the capacity of cancer cells to proliferate, migrate, metabolize and invade [26]; NDRG2 expression levels are negatively correlated with human cancer clinical and pathological conditions [26].…”