The nucleosome binding protein NSBP1 is highly expressed in human bladder cancer and promotes the proliferation and invasion of bladder cancer cells

Tumour Biol. 2011 Oct;32(5):931-9. doi: 10.1007/s13277-011-0195-0. Epub 2011 Jun 22.

Abstract

NSBP1 is a recently identified member of the HMGN protein family which binds to nucleosomes and regulates gene transcription through chromatin remodeling. In this study, we aimed to investigate the potential role of NSBP1 in human bladder cancer. We examined NSBP1 expression in 114 surgically removed bladder cancer specimens as well as 11 human bladder cell lines by immunohistochemistry and Western blot analysis, and found that NSBP1 level was correlated with the increased tumor grade and pathologic stage, and lymph node metastasis. RNAi-mediated knockdown of NSBP1 in EJ cells, a bladder cancer cell line that overexpressed NSBP1, resulted in moderate decrease of cell viability, moderate blockage of cell cycle at G2/M phase, and decreased cyclin B1 expression, but had no effects on apoptosis. Moreover, NSBP1 knockdown led to reduced activity of MMP-9 but not MMP-2. Taken together, these results suggest that NSBP1 promotes the viability of bladder cancer cells through increased cell proliferation but not decreased apoptosis, and increases the invasion ability of metastatic bladder cancer cells through the upregulation of MMP-9 activity. Our findings not only provide a molecular understanding of the role of NSBP1 in bladder cancer, but also suggest NSBP1 RNAi as a novel therapeutic approach for bladder cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Blotting, Western
  • Carcinoma, Transitional Cell / genetics
  • Carcinoma, Transitional Cell / metabolism*
  • Carcinoma, Transitional Cell / pathology*
  • Cell Movement / genetics
  • Cell Proliferation*
  • Cell Separation
  • Flow Cytometry
  • HMGN Proteins / biosynthesis*
  • HMGN Proteins / genetics
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Staging
  • Reverse Transcriptase Polymerase Chain Reaction
  • Trans-Activators / biosynthesis*
  • Trans-Activators / genetics
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / pathology*

Substances

  • HMGN Proteins
  • HMGN5 protein, human
  • Trans-Activators