DBCCR1 mediates death in cultured bladder tumor cells

Oncogene. 2004 Jan 8;23(1):82-90. doi: 10.1038/sj.onc.1206642.

Abstract

Chromosome 9, which is often partially or fully reduced to homozygosity in bladder cancer cells, harbors several tumor suppressor loci including deleted in bladder cancer chromosome region 1 (DBCCR1) at 9q32-33. To study DBCCR1 function, stable cell lines, inducible for DBCCR1 expression by tetracycline, were made, but the DBCCR1 protein was not expressed at detectable levels. To understand the fate of DBCCR1-expressing cells, human bladder tumor cells were transiently transfected with an expression vector containing DBCCR1 fused to enhanced green fluorescent protein (EGFP). Initially, DBCCR1-EGFP-expressing cells demonstrated diffuse cytoplasmic green fluorescence with nuclear exclusion patterns. After time, the intensity level of green fluorescence increased and a granular distribution of protein became visible in the cells. At this point, cells rounded up and detached from the tissue culture dish. Cells transfected with a control vector, containing only EGFP, and partial DBCCR1-EGFP fusion constructs did not demonstrate this behavior. DBCCR1-mediated cell death in cultured tumor cells was independent of caspase-3 activation and did not result in detectable DNA strand breaks by TUNEL staining that are hallmarks of the classical apoptotic pathway.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis*
  • Caspase 3
  • Caspases / physiology
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • In Situ Nick-End Labeling
  • Mice
  • NIH 3T3 Cells
  • Nerve Tissue Proteins
  • Tumor Suppressor Proteins / analysis
  • Tumor Suppressor Proteins / physiology*
  • Urinary Bladder Neoplasms / pathology*

Substances

  • BRINP1 protein, human
  • Cell Cycle Proteins
  • Nerve Tissue Proteins
  • Tumor Suppressor Proteins
  • CASP3 protein, human
  • Casp3 protein, mouse
  • Caspase 3
  • Caspases