title: Promoter hypermethylation of membrane type 3 matrix metalloproteinase is associated with cell migration in colorectal adenocarcinoma.
abstract: The gene MT3-MMP (also known as MMP16) encodes the membrane type 3 matrix metalloproteinase, which is a member of the matrix metalloproteinase (MMP) gene family. Several MMPs are associated with migration in colorectal cancer (CRC). However, the methylation status of the MT3-MMP promoter in CRC has not been reported. The methylation status and expression levels of MT3-MMP were investigated in primary tumor tissues and adjacent normal tissues in 105 patients with CRC, one normal colon cell line (CCD18Co), and three CRC cell lines (SW480, DLD-1, and LoVo) by quantitative methylation-specific PCR and real-time PCR. MT3-MMP was hypermethylated in 82 of 105 CRC tissues (78%), 30 of 105 adjacent normal tissues (29%), and two of 11 normal colon tissues (18%). MT3-MMP mRNA was significantly reduced in CRC compared with that in adjacent normal tissues (P < 0.05). The methylation-mediated downregulation of MT3-MMP was restored by treatment with 5-aza-2'-deoxycytidine in two CRC cell lines, and MT3-MMP promoter activity was significantly reduced by methylation. The knockdown of MT3-MMP induced cell migration, but overexpressed MT3-MMP reduced cell migration in CRC cells. These results demonstrate that the MT3-MMP promoter is frequently hypermethylated in CRC and that downregulation of MT3-MMP may be important for cell migration in CRC.
authors.affiliation: Institute of Human Genetics, Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea; Department of Pathology, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Ji Wook
authors.initials: JW
authors.lastname: Moon
authors.affiliation: Department of Biomedical Science, CHA University, Seoul, Republic of Korea.
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Institute of Human Genetics, Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Institute of Human Genetics, Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yong Woo
authors.initials: YW
authors.lastname: Lee
authors.affiliation: Institute of Human Genetics, Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jung Ok
authors.initials: JO
authors.lastname: Lee
authors.affiliation: Institute of Human Genetics, Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Nami
authors.initials: N
authors.lastname: Kim
authors.affiliation: Institute of Human Genetics, Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hye Jeong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Institute of Human Genetics, Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jung Seon
authors.initials: JS
authors.lastname: Seo
authors.affiliation: Department of General Surgery, Korea University Medical Center, Seoul, Republic of Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
authors.affiliation: Institute of Human Genetics, Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyeon Soo
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science, CHA University, Seoul, Republic of Korea.
authors.forename: Gi Jin
authors.initials: GJ
authors.lastname: Kim
authors.affiliation: Institute of Human Genetics, Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea. Electronic address: parksh@korea.ac.kr.
authors.forename: Sun-Hwa
authors.initials: SH
authors.lastname: Park
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000368:Aged; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D019175:DNA Methylation / Q000235:genetics*; D000077209:Decitabine; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D053513:Matrix Metalloproteinase 16 / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C507102:MMP16 protein, human; D034741:RNA, Small Interfering; D000077209:Decitabine; D053513:Matrix Metalloproteinase 16; D001374:Azacitidine
keywords: MMP16; MT3-MMP; colorectal cancer; hypermethylation; migration