Overexpression of N-Myc downstream-regulated gene 2 (NDRG2) regulates the proliferation and invasion of bladder cancer cells in vitro and in vivo

PLoS One. 2013 Oct 16;8(10):e76689. doi: 10.1371/journal.pone.0076689. eCollection 2013.

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 (χ(2)=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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Apoptosis
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Immunohistochemistry
  • Lentivirus / metabolism
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Nude
  • Middle Aged
  • Neoplasm Invasiveness
  • Proto-Oncogene Proteins c-myc / metabolism
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Urinary Bladder Neoplasms / enzymology
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / pathology*
  • Xenograft Model Antitumor Assays
  • Young Adult

Substances

  • NDRG2 protein, human
  • Proto-Oncogene Proteins c-myc
  • Tumor Suppressor Proteins
  • Green Fluorescent Proteins
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9

Grants and funding

This research work was financially supported by National Natural Science Foundation of China (31070681). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.