Abstract
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
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Clinical Trial
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Butylhydroxybutylnitrosamine / toxicity
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Carcinogens / toxicity
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Cell Cycle Proteins / biosynthesis*
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Cell Cycle Proteins / genetics
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DNA-Binding Proteins / biosynthesis*
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DNA-Binding Proteins / genetics
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Female
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Gene Deletion*
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Gene Expression Regulation, Neoplastic / drug effects
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Gene Expression Regulation, Neoplastic / genetics
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Genetic Predisposition to Disease*
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HEK293 Cells
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Heterozygote
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Humans
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Male
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Mice
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Mice, Knockout
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Prostatic Neoplasms / chemically induced
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Prostatic Neoplasms / genetics
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Prostatic Neoplasms / metabolism*
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Prostatic Neoplasms / pathology
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Tumor Suppressor Proteins / biosynthesis*
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Tumor Suppressor Proteins / genetics
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Urinary Bladder Neoplasms / chemically induced
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Urinary Bladder Neoplasms / genetics
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Urinary Bladder Neoplasms / metabolism*
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Urinary Bladder Neoplasms / pathology
Substances
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Carcinogens
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Cell Cycle Proteins
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DNA-Binding Proteins
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LZTS2 protein, human
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LZTS2 protein, mouse
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Tumor Suppressor Proteins
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Butylhydroxybutylnitrosamine