title: Reduced canine BRCA2 expression levels in mammary gland tumors.
abstract: BACKGROUND
  Mammary tumors are the most common tumor type in intact female dogs. Recently, the breast cancer 2 early onset (BRCA2) gene was proposed to be associated with tumorigenesis in dogs. The expression level of BRCA2 is important for its DNA repair function in mammalian cells, and its expression level is linked to tumorigenesis in mammary tissue. However, the expression of canine BRCA2 in mammary tumors is unclear.
  
  
  RESULTS
  BRCA2 mRNA levels were compared between seven mammary gland samples and seventeen mammary tumor samples isolated from dogs. The expression level of canine BRCA2 in mammary tumor samples was lower than levels in mammary gland samples. We attempted to identify why the BRCA2 expression level was decreased in mammary tumor samples by promoter sequencing analysis; however, we did not find any mutations in the canine BRCA2 promoter that altered BRCA2 transcription levels. We did detect two types of BRCA2 splice variants in 8 mammary tumor samples. One of the variants induced a frame-shift mutation that could lead to nonsense-mediated mRNA decay, a ubiquitous cellular mechanism that eliminates mRNA containing a premature termination codon.
  
  
  CONCLUSIONS
  Reduced expression of canine BRCA2 mRNA in mammary tumor samples is a possible mechanism to explain mammary tumor development in dogs. One possible reason for reduced BRCA2 mRNA levels in these tumor samples was nonsense-mediated mRNA decay, not mutations in the BRCA2 promoter region. While it remains unclear why canine BRCA2 expression levels are reduced in mammary tumor samples, this study found that the expression level of BRCA2 was associated with canine mammary tumorigenesis.
authors.affiliation: Laboratory of Veterinary Biochemistry, School of Veterinary Medicine, Kitasato University, Aomori, 034-8628, Japan. yyoshika@vmas.kitasato-u.ac.jp.
authors.forename: Yasunaga
authors.initials: Y
authors.lastname: Yoshikawa
authors.affiliation: Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, 060-0818, Japan. mmorimat@vetmed.hokudai.ac.jp.
authors.forename: Masami
authors.initials: M
authors.lastname: Morimatsu
authors.affiliation: Department of Basic Science, School of Veterinary Nursing and Technology, Nippon Veterinary and Life Science University, Tokyo, 180-8602, Japan. kochiai@nvlu.ac.jp.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ochiai
authors.affiliation: Department of Biological Resources, Integrated Center for Science, Ehime University, Ehime, 791-0295, Japan. oonumat@m.ehime-u.ac.jp.
authors.forename: Toshina
authors.initials: T
authors.lastname: Ishiguro-Oonuma
authors.affiliation: Laboratory of Veterinary Radiology and Radiation Biology, School of Veterinary Medicine, Kitasato University, Aomori, 034-8628, Japan. wada@vmas.kitasato-u.ac.jp.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Wada
authors.affiliation: Laboratory of Veterinary Biochemistry, School of Veterinary Medicine, Kitasato University, Aomori, 034-8628, Japan. orino@vmas.kitasato-u.ac.jp.
authors.forename: Koichi
authors.initials: K
authors.lastname: Orino
authors.affiliation: Laboratory of Veterinary Biochemistry, School of Veterinary Medicine, Kitasato University, Aomori, 034-8628, Japan. watanabe@vmas.kitasato-u.ac.jp.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D024682:BRCA2 Protein / Q000235:genetics / Q000378:metabolism*; D004283:Dog Diseases / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D024682:BRCA2 Protein; D020033:Protein Isoforms; D012333:RNA, Messenger