title: Oncogenic Role of BOLL in Colorectal Cancer.
abstract: BACKGROUND
  Boule-like RNA-binding protein (BOLL protein) is the progenitor of the Deleted in Azoospermia (DAZ) gene family. To date, previous studies have focused on the reproductive function of BOLL. While we were identifying new DNA methylation biomarkers for colorectal cancer (CRC), we found that BOLL protein was overexpressed in CRC.
  
  
  OBJECTIVE
  The aim of this study was to determine the role of BOLL in CRC by epigenetic and functional studies in vivo and in vitro.
  
  
  METHODS
  BOLL promoter methylation and expression were determined by MethyLight, RT-PCR, Western blot, and immunohistochemistry. The functional role of BOLL in CRC was evaluated by cell proliferation, colony formation, migration and invasion, cell cycle status, and tumor growth in a xenograft model.
  
  
  RESULTS
  BOLL promoter methylation was enhanced in CRC tissues compared with normal colorectal tissues [97/124 (78 %) vs. 2/124 (2 %)]. However, the mean immunoreactivity score of CRC tissues and paired adjacent normal tissues was 8.15 ± 0.18 (SD) and 3.35 ± 0.19 (SD), respectively (p < 0.01). No significant association was observed between immunoreactivity score and clinicopathological parameters, including age, gender, tumor size, tumor differentiation, and tumor node metastasis stage. Expression of BOLL in CRC cell lines significantly enhanced cell proliferation (p < 0.01), colony formation (p < 0.01), and migration (p < 0.01). In BOLL-expressing cells, the percentage of cells in S-phase of the cell cycle was significantly increased. Tumor volume in BOLL xenografted mice was significantly enhanced after subcutaneous implantation (p < 0.01).
  
  
  CONCLUSIONS
  Our study demonstrated an oncogenic role of BOLL in CRC despite tumor-specific promoter hypermethylation.
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-dong 50, Gangnam-gu, Seoul, 135-710, Republic of Korea, doc0708@gmail.com.
authors.forename: Ki Joo
authors.initials: KJ
authors.lastname: Kang
authors.forename: Jeung Hui
authors.initials: JH
authors.lastname: Pyo
authors.forename: Kyung Ju
authors.initials: KJ
authors.lastname: Ryu
authors.forename: Sung Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Ha
authors.forename: Kyu
authors.initials: K
authors.lastname: Choi
authors.forename: Sung Noh
authors.initials: SN
authors.lastname: Hong
authors.forename: Byung-Hoon
authors.initials: BH
authors.lastname: Min
authors.forename: Dong Kyung
authors.initials: DK
authors.lastname: Chang
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Son
authors.forename: Poong-Lyul
authors.initials: PL
authors.lastname: Rhee
authors.forename: Jae J
authors.initials: JJ
authors.lastname: Kim
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Kim
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011401:Promoter Regions, Genetic; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection
chemical_list: C481351:BOLL protein, human; D014408:Biomarkers, Tumor; D016601:RNA-Binding Proteins