贲门腺癌中RASSF1A基因甲基化与cyclin D1表达的关系
Relationship between RASSF1A gene methylation and the expression of cyclin D1 in gastric cardiac adenocarci-noma
摘 要
目的: 探讨贲门腺癌(gastric cardiac adenocarcinoma,GCA)中RASSF1A基因的甲基化状态及其与cyclin D1蛋白表达之间的相关性。方法: 分别应用甲基化特异性PCR(mothylation-specific PCR,MSP)方法和免疫组织化学SP法检测贲门腺癌组织及相应癌旁组织的RASSF1A基因甲基化情况和cyclin D1蛋白表达情况。结果: 92例贲门腺癌组织中有54例RASSF1A发生了甲基化,甲基化率为58.7%,显著高于癌旁正常组织(P<0.001)。Ⅲ期和Ⅳ期贲门腺癌患者中RASSF1A基因发生甲基化的比率显著高于Ⅰ期和Ⅱ期患者(P<0.05)。92例贲门腺癌组织中有72例(78.3%)cyclin D1蛋白表达阳性,与相应癌旁正常组织比较,cyclin D1在贲门癌组织中的表达显著升高(P<0.001);且随肿瘤分化程度的降低,cyclin D1的阳性表达率明显升高(P<0.05)。RASSF1A基因在贲门腺癌中的高甲基化与cyclin D1蛋白表达之间有明显的相关性(P<0.05)。结论: RASSF1A基因启动子区的高甲基化以及cyclin D1蛋白的过表达可能参与了贲门腺癌的发生发展过程。
贲门
DNA甲基化
基因,肿瘤抑制
细胞周期蛋白D1
基因,RASSF1A
Stomach neoplasms
Cardia
DNA methylation
Genes,tumor suppressor
Cyclin D1
Gene,RASSF1A
Abstract
Objective: To investigate the relationship between RASSF1A gene methylation and the expression of cyclin D1 in gastric cardiac adenocarcinoma (GCA). Methods: The methylation of the 5' CpG island of RASSF1A was detected by methylation-specific PCR (MSP) and the expression of cyclin D1 was determined by immunohistochemical method in GCA tissues and corresponding paracancerous normal tissues. Results: RASSF1A was methylated in 54/92(58.7%) tumor specimens, which was significantly higher than that in corresponding normal tissues (P<0.001). Methylation frequencies of stages Ⅲ and Ⅳ tumor tissues were significantly higher than those in stageⅠand Ⅱ tumor tissues (P<0.05). Positive immunostaining of cyclin D1 was detected in 72/92(78.3%) tumor tisssues, which was significantly higher than that in corresponding normal tissues (P<0.001). The positivity of cyclin D1 was significantly increased with the decrease in the differentiation degree of GCA (P<0.05). Hypermethylation of RASSF1A was correlated with the expression of cyclin D1 in GCA(P<0.05).Conclusion: The hypermethylation in the promoter region of RASSF1A gene and over-expression of cyclin D1 may be involved in the tumorigenesis and progress of GCA.
中图分类号 R735.2 DOI 10.3781/j.issn.1000-7431.2009.02.014
所属栏目 临床研究
基金项目 河北省科技厅科技攻关项目(编号:052761163);河北省强势特色学科基金资助项目(编号:冀教高[2005]52号)
收稿日期 2008/4/11
修改稿日期 2008/5/13
网络出版日期
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引用该论文: GUO Wei,YANG Zhi-bin,FAN Li-qiao,KUANG Gang,DONG Zhi-ming. Relationship between RASSF1A gene methylation and the expression of cyclin D1 in gastric cardiac adenocarci-noma[J]. Tumor, 2009, 29(2): 164～167
郭炜,杨植彬,范立侨,邝钢,董稚明. 贲门腺癌中RASSF1A基因甲基化与cyclin D1表达的关系[J]. 肿瘤, 2009, 29(2): 164～167
被引情况:
【1】郭炜,朱铁年,董稚明,张明慧,崔蕾, "Gadd45G基因在食管鳞癌组织中的异常甲基化及表达",肿瘤 33, 74-80(2013)
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参考文献
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【2】SHIVAKUMAR L, MINNA J, SAKAMAKI T, et al. The RASSF1A tumor suppressor blocks cell cycle progression and inhibits cyclin D1 accumulation[J]. Mol Cell Biol, 2002, 22(12):4309-4318.
【3】HERMAN J G, GRAFF J R, MYOHANEN S, et al. Methylation-specific PCR:a novel PCR assay for methylation status of CpG islands[J]. Proc Natl Acad Sci USA, 1996, 93(18):9821-9826.
【4】KHOKHLATCHEV A, RABIZADEH S, XAVIER R, et al. Identification of a novel Ras-regulated proapoptotic pathway[J]. Curr Biol, 2002, 12(4):253-265.
【5】DAMMANN R, TAKAHASHI T, PFEIFER G P, et al. The CpG island of the novel tumor suppressor gene RASSF1A is intensely-methylated in primary small cell lung carcinomas[J]. Oncogene, 2001, 20(27):3563-3567.
【6】AGATHANGGELOU A, HONORIO S, MACARTNEY D P, et al. Methylation associated inactivation of RASSF1A from region 3p21.3 in lung, breast and ovarian tumours[J]. Oncogene, 2001, 20(12):1509-1518.
【7】LO K W, KWONG J, HUI A B, et al. High frequency of promoter hypermethylation of RASSF1A in nasopharyngeal carcinoma[J]. Cancer Res, 2001, 61(10):3877-3881.
【8】LI J Y, ERSHOW A G, CHEN Z J, et al. A case-control study of cancer of the esophageal and gastric cardia in Linxian[J]. Int J Cancer, 1989, 43(5):755-761.
【9】ZHANG Y J, AHSAN H, CHEN Y, et al. High frequency of promoter hypermethylation of RASSF1A and p16 and its relationship to aflatoxin B12DNA adduct levels in human hepatocellular carcinoma[J]. Mol Carcinog, 2002, 35(2):85-92.
【10】BYUN D S, LEE M G, CHAE K S, et al. Frequent epigenetic inactivation of RASSF1A by aberrant promoter hypermethylation in human gastric adenocarcinoma[J]. Cancer Res, 2001, 61(19):7034-7038.
【11】VAN-ENGELAND M, ROEMEN G M, BRINK M, et al. K-ras mutations and RASSF1A promoter methylation in colorectal cancer[J]. Oncogene, 2002, 21(23):3792-3795.
【12】KUROKI T, TRAPASSO F, YENDAMURI S, et al. Promoter hypermethylation of RASSF1A in esophageal squamous cell carcinoma[J]. Clin Cancer Res, 2003, 9(4):1441-1445.
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