Deletion of Leucine Zipper Tumor Suppressor 2 (Lzts2) Increases Susceptibility to Tumor Development

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. Background: The leucine zipper putative tumor suppressor 2 (LZTS2) has been speculated to be a tumor suppressor for more than a decade. Results: Deletion of Lzts2 increases the susceptibility to spontaneous and carcinogen-induced tumor development in mice. Conclusion: LZTS2 functions as a tumor susceptibility gene. Significance: Identifying a novel role for LZTS2 in tumorigenesis in a novel mouse model.