Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10897632 | Cancer Genetics | 2015 | 10 Pages |
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 (PÂ <Â 0.05). The methylation-mediated downregulation of MT3-MMP was restored by treatment with 5-aza-2â²-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.
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Authors
Ji Wook Moon, Jong-Ho Choi, Soo Kyung Lee, Yong Woo Lee, Jung Ok Lee, Nami Kim, Hye Jeong Lee, Jung Seon Seo, Jin Kim, Hyeon Soo Kim, Gi Jin Kim, Sun-Hwa Park,