인간 대장암에서 Bone Morphogenetic Protein 2 유전자의 후향적 변이에 관한 연구
A Study of Epigenetic Alteration of the Bone Morphogenetic Protein-2 Gene in Human Colorectal Cancer
장용선, 장준혁, 구지회, 김경래, 최선근, 김광, 윤민영,
소속 상세정보
장용선 ( Jang Yong-Sun )
인하대학교 의학전문대학원 외과학교실
장준혁 ( Jang Jun-Hyuk )
인하대학교 의과대학 생화학교실
구지회 ( Koo Ji-Hoe )
인하대학교 의과대학 외과학교실
김경래 ( Kim Kyung-Rae )
인하대학교 의과대학 외과학교실
최선근 ( Choi Sun-Keun )
인하대학교 의과대학 외과학교실
김광 ( Kim Kwang )
인하대학교 의학전문대학원 외과학교실
윤민영 ( Yun Min-Young )
미즈메디병원 외과
KMID : 0356720100260010053
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.
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.
키워드
대장암; BMP-2; 대장암 형성
Colorectal cancer; BMP-2; Colorectal carcinogenesis
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