| Science Letters：IGFBP7 plays a potential tumor suppressor role against colorectal carcinogenesis with its expression associated with DNA hypomethylation of exon 1 |
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| 作者姓名： | Ruan WJ Lin J Xu EP Xu FY Ma Y Deng H Huang Q Lv BJ Hu H Cui J Di MJ Dong JK Lai MD |
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| 作者单位： | [1]Department of Pathology, School of Medicine, Zhejiang University, Hangzhou 310031, China [2]Department of Pathology, the People ＂s No. 1 Hospital of Xiaoshan, Hangzhou 311201, China [3]Center for Disease Control and Prevention of Xiaoshan, Hangzhou 311201, China [4]Department of Basic Medicine, Hangzhou Teachers College, Hangzhou 310036, China |
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| 摘 要： | Insulin-like growth factor binding-protein-7 （IGFBP7） was obtained from our previous colonic adenocarcinoma （CRC） and normal mucosa suppression subtraction hybridization （SSH） cDNA libraries. By RT-PCR and immunohistochemistry, we found that IGFBP7 was overexpressed in CRC tissue compared to normal tissue. However, our in vitro experiments performed in 10 CRC cell lines showed that IGFBP7 expressed only in SW480 and Caco2 cell lines, which implied an underlying reversible regulatory mechanism. Using methylation-specific PCR （MSP） and bisulfite sodium PCR （BSP）, we found that its expression was associated with DNA hypomethylation of exonl. This was further supported by the in vitro study which showed restored IGFBP7 expression after demethylation agent 5-aza-2＇-deoxycytidine treatment. Correlation analysis between IGFBP7 expression and prognosis indicated that overexpression of IGFBP7 in CRC tissue correlated with favourable survival. Investigation of the functional role of IGFBP7 through transfection studies showed that IGFBP7 protein could inhibit growth rate, decrease colony formation activity, and induce apoptosis in RKO and SW620 cells, suggesting it a potential tumor suppressor protein in colorectal carcinogenesis. In conclusion, our study clearly demonstrated that IGFBP7 plays a potential tumor suppressor role against colorectal carcinogenesis and its expression is associated with DNA hypomethylation of exon 1.
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| 关 键 词： | IGFBP7 结直肠癌 甲基化作用 肿瘤抑制因子 结肠腺癌 |
| 收稿时间： | 2006-09-26 |
| 修稿时间： | 2006-10-13 |
IGFBP7 plays a potential tumor suppressor role against colorectal carcinogenesis with its expression associated with DNA hypomethylation of exon 1 |
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| Ruan WJ,Lin J,Xu EP,Xu FY,Ma Y,Deng H,Huang Q,Lv BJ,Hu H,Cui J,Di MJ,Dong JK,Lai MD.IGFBP7 plays a potential tumor suppressor role against colorectal carcinogenesis with its expression associated with DNA hypomethylation of exon 1[J].Journal of Zhejiang University Science,2006,7(11):929-932. |
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| Authors: | Wen-jing Ruan Jie Lin En-ping Xu Fang-ying Xu Yu Ma Hong Deng Qiong Huang Bing-jian Lv Hu Hu Jing Cui Mei-juan Di Jian-kang Dong Mao-de Lai |
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| Institution: | (1) Department of Pathology, School of Medicine, Zhejiang University, Hangzhou, 310031, China;(2) Department of Pathology, the People’s No. 1 Hospital of Xiaoshan, Hangzhou, 311201, China;(3) Center for Disease Control and Prevention of Xiaoshan, Hangzhou, 311201, China;(4) Department of Basic Medicine, Hangzhou Teachers College, Hangzhou, 310036, China |
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| Abstract: | Insulin-like growth factor binding-protein-7 (IGFBP7) was obtained from our previous colonic adenocarcinoma (CRC) and normal mucosa suppression subtraction hybridization (SSH) cDNA libraries. By RT-PCR and immunohistochemistry, we found that IGFBP7 was overexpressed in CRC tissue compared to normal tissue. However, our in vitro experiments performed in 10 CRC cell lines showed that IGFBP7 expressed only in SW480 and Caco2 cell lines, which implied an underlying reversible regulatory mechanism. Using methylation-specific PCR (MSP) and bisulfite sodium PCR (BSP), we found that its expression was associated with DNA hypomethylation of exon1. This was further supported by the in vitro study which showed restored IGFBP7 expression after demethylation agent 5-aza-2'-deoxycytidine treatment. Correlation analysis between IGFBP7 expression and prognosis indicated that overexpression of IGFBP7 in CRC tissue correlated with favourable survival. Investigation of the func-tional role of IGFBP7 through transfection studies showed that IGFBP7 protein could inhibit growth rate, decrease colony for-mation activity, and induce apoptosis in RKO and SW620 cells, suggesting it a potential tumor suppressor protein in colorectal carcinogenesis. In conclusion, our study clearly demonstrated that IGFBP7 plays a potential tumor suppressor role against colo-rectal carcinogenesis and its expression is associated with DNA hypomethylation of exon 1. |
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| Keywords: | IGFBP7 (Insulin-like growth factor binding-protein-7) Colorectal cancer Tumor suppressor protein Methylation |
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