Deletion of leucine zipper tumor suppressor 2 (Lzts2) increases susceptibility to tumor development

J Biol Chem. 2013 Feb 8;288(6):3727-38. doi: 10.1074/jbc.M112.417568. Epub 2012 Dec 28.


Using an Lzts2 knock-out mouse model, we characterized the biological role of Lzts2 in tumorigenesis. Both heterozygous and homozygous deletion of the Lzts2-targeted allele in mice shows an increased incidence in spontaneous tumor development, although Lzts2 homozygous knock-out mice show significantly higher incidences than heterozygous mice. Treatment of Lzts2-deficient mice with a carcinogen, N-butyl-N-(4-hydroxybutyl) nitrosamine, increases the susceptibility to N-butyl-N-(4-hydroxybutyl) nitrosamine-induced bladder carcinoma development. Examination of human prostate cancer tissue specimens shows a reduction of LZTS2 protein expression in prostate cancer cells. Further analyses of mouse embryonic fibroblasts isolated from Lzts2 knock-out embryos show that loss of Lzts2 enhances cell growth. These data provide the first line of evidence demonstrating that deletion of Lzts2 increases susceptibility to spontaneous and carcinogen-induced tumor development.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Butylhydroxybutylnitrosamine / toxicity
  • Carcinogens / toxicity
  • Cell Cycle Proteins / biosynthesis*
  • Cell Cycle Proteins / genetics
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / genetics
  • Female
  • Gene Deletion*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / genetics
  • Genetic Predisposition to Disease*
  • HEK293 Cells
  • Heterozygote
  • Humans
  • Male
  • Mice
  • Mice, Knockout
  • Prostatic Neoplasms / chemically induced
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Tumor Suppressor Proteins / biosynthesis*
  • Tumor Suppressor Proteins / genetics
  • Urinary Bladder Neoplasms / chemically induced
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / pathology


  • Carcinogens
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • LZTS2 protein, human
  • LZTS2 protein, mouse
  • Tumor Suppressor Proteins
  • Butylhydroxybutylnitrosamine