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KMID : 0356720100260010053
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Journal of the Korean Society of Coloproctology
2010 Volume.26 No. 1 p.53 ~ p.61
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A Study of Epigenetic Alteration of the Bone Morphogenetic Protein-2 Gene in Human Colorectal Cancer
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Jang Yong-Sun
Jang Jun-Hyuk
Koo Ji-Hoe
Kim Kyung-Rae
Choi Sun-Keun
Kim Kwang
Yun Min-Young
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Abstract
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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.
Conclusions: 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.
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KEYWORD
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Colorectal cancer, BMP-2, Colorectal carcinogenesis
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