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.
| Original language | English |
|---|---|
| Pages (from-to) | 261-270 |
| Number of pages | 10 |
| Journal | Cancer genetics |
| Volume | 208 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2015 May 1 |
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Keywords
- Colorectal cancer
- Hypermethylation
- Migration
- MMP16
- MT3-MMP
ASJC Scopus subject areas
- Cancer Research
- Genetics
- Molecular Biology
Cite this
Promoter hypermethylation of membrane type 3 matrix metalloproteinase is associated with cell migration in colorectal adenocarcinoma. / Moon, Ji Wook; Choi, Jong Ho; Lee, Soo Kyung; Lee, Yong Woo; Lee, Jung Ok; Kim, Nami; Lee, Hye Jeong; Seo, Jung Seon; Kim, Jin; Kim, Hyeon Soo; Kim, Gi Jin; Park, Sun-Hwa.
In: Cancer genetics, Vol. 208, No. 5, 01.05.2015, p. 261-270.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Promoter hypermethylation of membrane type 3 matrix metalloproteinase is associated with cell migration in colorectal adenocarcinoma
AU - Moon, Ji Wook
AU - Choi, Jong Ho
AU - Lee, Soo Kyung
AU - Lee, Yong Woo
AU - Lee, Jung Ok
AU - Kim, Nami
AU - Lee, Hye Jeong
AU - Seo, Jung Seon
AU - Kim, Jin
AU - Kim, Hyeon Soo
AU - Kim, Gi Jin
AU - Park, Sun-Hwa
PY - 2015/5/1
Y1 - 2015/5/1
N2 - 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.
AB - 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.
KW - Colorectal cancer
KW - Hypermethylation
KW - Migration
KW - MMP16
KW - MT3-MMP
UR - http://www.scopus.com/inward/record.url?scp=84930572619&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84930572619&partnerID=8YFLogxK
U2 - 10.1016/j.cancergen.2015.04.009
DO - 10.1016/j.cancergen.2015.04.009
M3 - Article
VL - 208
SP - 261
EP - 270
JO - Cancer genetics
JF - Cancer genetics
SN - 2210-7762
IS - 5
ER -