A Study of Epigenetic Alteration of the Bone Morphogenetic Protein-2 Gene in Human Colorectal Cancer.
10.3393/jksc.2010.26.1.53
- Author:
Yong Sun JANG
1
;
Kwang KIM
;
Min Young YUN
;
Sun Keun CHOI
;
Kyung Rae KIM
;
Jun Hyeog JANG
;
Ji Hoe KOO
Author Information
1. Department of Surgery, Inha University School of Medicine, Incheon, Korea.
- Publication Type:Original Article
- Keywords:
Colorectal cancer;
BMP-2;
Colorectal carcinogenesis
- MeSH:
Bone Morphogenetic Proteins;
Cell Line;
Colon;
Colorectal Neoplasms;
CpG Islands;
DNA Methylation;
Epigenomics;
Gene Expression;
Humans;
Methylation;
Mucins;
Polymerase Chain Reaction;
Promoter Regions, Genetic;
Rectal Neoplasms
- From:Journal of the Korean Society of Coloproctology
2010;26(1):53-61
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta family and play an important role in cellular growth. Recent reports suggest that exogenous bone morphogenetic protein-2 (BMP-2) acts as an antiproliferative agent in a variety of cell lines. We will study whether BMP-2 is altered in human colorectal cancer. METHODS: We analyzed 40 colorectal cancer cases and 6 colorectal cancer cell lines by using reverse transcription-polymerase chain reaction (RT-PCR) to determine the expression of BMP-2. RESULTS: Thirteen of 40 colorectal cancers (33%) and 3 of 6 colorectal cancer cell lines (50%) revealed decreased expression of BMP-2. The rates of decreased expression were 0% (0/7), 42.1% (8/19), 28.6% (2/7), 33.3% (2/6), and 100% (1/1) in stages I, II, III, and IV, respectively. Histologically, the rates were 33.3% (2/6), 32.2% (10/21), 50% (1/2), and 0% (0/1) in well-differentiated, moderately-differentiated, poorly-differentiated and mucinous cancers, respectively. As for location, the rates for colon and rectal cancers were 27.8% (5/18) and 36.4% (8/22), respectively. We identified methylation in the CpG island of the BMP-2 gene in 60% of colorectal cancer cells and in 50% of colorectal cancer cell lines. The 13 cases without BMP-2 gene expression showed no significant correlation with clinicopathological factors. Epigenetic silencing through DNA methylation is one of the key steps during carcinogenesis. CONCLUSION: We found, through an analysis using the methylation-specific polymerase chain reaction technique, CpG island methylation of the BMP-2 promoter region in colorectal cancer. Thus, aberrant BMP-2 methylation and the resultant loss of BMP-2 expression may be related to colorectal carcinogenesis.
