title: Tumor suppressive effects of bromodomain-containing protein 7 (BRD7) in epithelial ovarian carcinoma.
abstract: OBJECTIVE
  Bromodomain-containing protein 7 (BRD7), which is a subunit of SWI/SNF complex, has been recently suggested as a novel tumor suppressor in several cancers. In this study, we investigated the tumor suppressive effect of BRD7 in epithelial ovarian cancer.
  
  
  METHODS
  We analyzed the expression of BRD7 in human ovarian tissues with real-time PCR. To investigate the functional role of BRD7, we transfected ovarian cancer cells (A2780 and SKOV3) with BRD7 plasmid and checked the cell viability, apoptosis, and invasion. The activities of BRD7 in the signaling pathways associated with carcinogenesis were also tested. In addition, we used the orthotopic mouse model for ovarian cancer to evaluate tumor growth-inhibiting effect by administration of BRD7 plasmid.
  
  
  RESULTS
  The BRD7 expression was downregulated in the ovarian cancer tissues compared with normal (P < 0.05), high-grade serous cancer exhibited significantly decreased expression of BRD7 compared with low-grade (P < 0.01) serous cancer. Transfection of BRD7 plasmid to A2780 (p53-wild) or SKOV3 (p53-null) ovarian cancer cells showed the tumor suppressive effects assessed by cell viability, apoptosis, and invasion assay and especially significantly decreased tumor weight in orthotopic mouse model (A2780). Moreover, we found that tumor suppressive effects of BRD7 are independent to the presence of p53 activity in ovarian cancer cells. BRD7 negatively regulated β-catenin pathway, resulting in decreased its accumulation in the nucleus.
  
  
  CONCLUSIONS
  These results suggested that BRD7 acts as a tumor suppressor in epithelial ovarian cancers independently of p53 activity, via negative regulation of β-catenin pathway.
authors.affiliation: Authors' Affiliations: Department of Obstetrics & Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine; and Department of Pathology, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine, Seoul, Korea.
authors.forename: Young-Ae
authors.initials: YA
authors.lastname: Park
authors.forename: Jeong-Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Hye-Sun
authors.initials: HS
authors.lastname: Kim
authors.forename: Yoo-Young
authors.initials: YY
authors.lastname: Lee
authors.forename: Tae-Joong
authors.initials: TJ
authors.lastname: Kim
authors.forename: Chel Hun
authors.initials: CH
authors.lastname: Choi
authors.forename: Jung-Joo
authors.initials: JJ
authors.lastname: Choi
authors.forename: Hye-Kyung
authors.initials: HK
authors.lastname: Jeon
authors.forename: Young Jae
authors.initials: YJ
authors.lastname: Cho
authors.forename: Ji Yoon
authors.initials: JY
authors.lastname: Ryu
authors.forename: Byoung-Gie
authors.initials: BG
authors.lastname: Kim
authors.forename: Duk-Soo
authors.initials: DS
authors.lastname: Bae
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D000077216:Carcinoma, Ovarian Epithelial; D002469:Cell Separation; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D000092468:Bromodomain Containing Proteins
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C485694:BRD7 protein, human; D000092468:Bromodomain Containing Proteins