title: Overexpression of mucin 13 due to promoter methylation promotes aggressive behavior in ovarian cancer cells.
abstract: OBJECTIVE
  Recent discoveries suggest that aberrant DNA methylation provides cancer cells with advanced metastatic properties. However, the precise regulatory mechanisms controlling metastasis genes and their role in metastatic transformation are largely unknown. To address epigenetically-regulated gene products involved in ovarian cancer metastasis, we examined the mechanisms regulating mucin 13 (MUC13) expression and its influence on aggressive behaviors of ovarian malignancies.
  
  
  METHODS
  We injected SK-OV-3 ovarian cancer cells peritoneally into nude mice to mimic human ovarian tumor metastasis. Overexpression of MUC13 mRNA was detected in metastatic implants from the xenografts by expression microarray analysis and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The DNA methylation status within the MUC13 promoter region was determined using bisulfite sequencing PCR and quantitative methylation-specific PCR. We evaluated the effects of exogenous MUC13 on cell invasion and migration using in vitro transwell assays.
  
  
  RESULTS
  MUC13 mRNA expression was up-regulated, and methylation of specific CpG sites within the promoter was reduced in the metastatic implants relative to those in wild-type SK-OV-3 cells. Addition of a DNA methyltransferase inhibitor to SK-OV-3 cells induced MUC13 expression, thereby implying epigenetic regulation of MUC13 by promoter methylation. MUC13 overexpression increased migration and invasiveness, compared to control cells, suggesting aberrant up-regulation of MUC13 is strongly associated with progression of aggressive behaviors in ovarian cancer.
  
  
  CONCLUSIONS
  We provide novel evidence for epigenetic regulation of MUC13 in ovarian cancer. We suggest that the DNA methylation status within the MUC13 promoter region may be a potential biomarker of aggressive behavior in ovarian cancer.
authors.affiliation: Department of Biochemistry, School of Medicine, Ewha Womans University, Seoul, Korea.
authors.forename: Hye Youn
authors.initials: HY
authors.lastname: Sung
authors.affiliation: College of Pharmacy, Sunchon National University, Suncheon, Korea.
authors.forename: Ae Kyung
authors.initials: AK
authors.lastname: Park
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Ewha Womans University, Seoul, Korea. goodmorning@ewha.ac.kr.
authors.forename: Woong
authors.initials: W
authors.lastname: Ju
authors.affiliation: Department of Biochemistry, School of Medicine, Ewha Womans University, Seoul, Korea. ahnj@ewha.ac.kr.
authors.forename: Jung-Hyuck
authors.initials: JH
authors.lastname: Ahn
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts / Q000378:metabolism; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009077:Mucins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D009361:Neoplasm Invasiveness / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: C429552:MUC13 protein, human; D009077:Mucins; D012333:RNA, Messenger
keywords: DNA methylation; MUC13; Ovarian cancer; mouse xenograft