title: Ovca1 regulates cell proliferation, embryonic development, and tumorigenesis.
abstract: Loss of OVCA1/DPH2L1 correlates with ovarian and breast cancer. To study its in vivo role, we generated Ovca1 mutant alleles in mice. Ovca1 heterozygotes spontaneously develop cancer. Ovca1 mutant mice die during embryonic development and at birth with developmental delay and defects in multiple organ systems. Cell proliferation defects were observed in Ovca1 mutant mouse embryonic fibroblasts (MEFs). p53 deficiency can rescue these Ovca1 mutant MEF proliferation defects and partially rescue Ovca1 mutant embryonic phenotypes. Furthermore, Ovca1; p53 double heterozygotes developed tumors quicker than p53 heterozygotes and with an increased carcinoma incidence. Multiple tumor burden in Ovca1 heterozygotes that were also p53 deficient was significantly higher than in p53 homozygous mutants. These in vivo findings demonstrate that Ovca1 is a tumor suppressor that can modify p53-induced tumorigenesis and suggest that it acts as a positive regulator for cell cycle progression. The close linkage of OVCA1 and p53 on human Chromosome 17 suggests that coordinated loss may be an important mechanism for the evolution of ovarian, breast, and other tumor phenotypes.
authors.affiliation: Department of Molecular Genetics, University of Texas, MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Chen
authors.forename: Richard R
authors.initials: RR
authors.lastname: Behringer
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002455:Cell Division / Q000235:genetics*; D000013:Congenital Abnormalities / Q000235:genetics; D005314:Embryonic and Fetal Development / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D051379:Mice; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C485679:Dph1 protein, mouse; D015778:Minor Histocompatibility Antigens; D025521:Tumor Suppressor Proteins