| A Study of Epigenetic Alteration of the Bone Morphogenetic Protein-2 Gene in Human Colorectal Cancer. |
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Jang, Yong Sun , Kim, Kwang , Yun, Min Young , Choi, Sun Keun , Kim, Kyung Rae , Jang, Jun Hyeog , Koo, Ji Hoe |
1Department of Surgery, Inha University School of Medicine, Incheon, Korea.
2Department of Surgery, Mizmedi Hospital, Seoul, Korea.
3Department of Biochemistry, Inha University School of Medicine, Incheon, Korea.
4Department of Surgery, Incheon Medical Center, Incheon, Korea. killoth@yahoo.com |
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| 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. |
| Key Words:
Colorectal cancer; BMP-2; Colorectal carcinogenesis |
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