title: Deletion of leucine zipper tumor suppressor 2 (Lzts2) increases susceptibility to tumor development.
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.
authors.affiliation: Department of Urology, Stanford University School of Medicine, Stanford, California 94305-5328, USA.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Johnson
authors.forename: Richard
authors.initials: R
authors.lastname: Luong
authors.forename: Suk Hyung
authors.initials: SH
authors.lastname: Lee
authors.forename: Yue
authors.initials: Y
authors.lastname: Peng
authors.forename: Atossa
authors.initials: A
authors.lastname: Shaltouki
authors.forename: Jane T
authors.initials: JT
authors.lastname: Lee
authors.forename: Dong
authors.initials: D
authors.lastname: Lin
authors.forename: Yuzhuo
authors.initials: Y
authors.lastname: Wang
authors.forename: Zijie
authors.initials: Z
authors.lastname: Sun
mesh_terms: D000818:Animals; D002085:Butylhydroxybutylnitrosamine / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D020022:Genetic Predisposition to Disease; D057809:HEK293 Cells; D006579:Heterozygote; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011471:Prostatic Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D002273:Carcinogens; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C440108:LZTS2 protein, human; C569000:LZTS2 protein, mouse; D025521:Tumor Suppressor Proteins; D002085:Butylhydroxybutylnitrosamine