title: MPP3 inactivation by promoter CpG islands hypermethylation in colorectal carcinogenesis.
abstract: BACKGROUND
  The Drosophila discs large tumor suppressor homologue-3 (MPP3), a putative tumor suppressor involved in cell adhesion and cell polarity, is frequently inactivated in several carcinomas due to promoter hypermethylation. The alteration of MPP3 methylation in colorectal carcinogenesis has not been investigated.
  
  
  OBJECTIVE
  To determine the role of inactivated MPP3 in colorectal tumorigenesis and the potential clinical application as a novel epigenetic marker.
  
  
  METHODS
  We measured MPP3 mRNA expression and promoter methylation in 6 colorectal cancer cell lines, 23 primary colorectal carcinomas and corresponding non-cancerous tissues. The correlations between MPP3 expression, DNA methylation and clinicopathological characteristics were evaluated.
  
  
  RESULTS
  Loss of MPP3 expression was observed in 2 of 6 (33.3%) colorectal cancer cell lines and 10 of 23 (43.5%) primary colorectal carcinomas. MPP3 promoter hypermethylation also occurred in the same colorectal cancer cell lines (SW1116 and LoVo) and 9 of 23 (39.1%) primary colorectal carcinomas. Among tumors loss of MPP3 mRNA expression, the promoter hypermethylation rate was 80%, which was significantly higher than tumors with over-expressed MPP3 (7.7%, P=0.001). After treated with 5-aza-dC, two cell lines (SW1116 and LoVo) revealed significant restoration of MPP3 expression. MPP3 promoter methylation was also significantly higher in advanced colorectal carcinoma (57.1%) compared with early stage tumor (11.1%).
  
  
  CONCLUSIONS
  These preliminary data suggested that epigenetic inactivation of MPP3 frequently occurred during the development of colorectal cancer and might also be a potential biomarker for molecular classification of colorectal cancer patients.
authors.affiliation: Department of Gastroenterology, the Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Feng
authors.forename: Kequan
authors.initials: K
authors.lastname: Chen
authors.forename: Shicai
authors.initials: S
authors.lastname: Ye
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Guoli
authors.initials: G
authors.lastname: Wei
authors.forename: Wenkai
authors.initials: W
authors.lastname: Tan
authors.forename: Si
authors.initials: S
authors.lastname: Cheng
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhang
authors.forename: Side
authors.initials: S
authors.lastname: Liu
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D019073:HT29 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: C116869:DLG3 protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors