Zhu Yi-Min, Huang Qiong, Lin Jie, Hu Yu, Chen Jian, Lai Mao-De
Department of Epidemiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310006, China.
Int J Colorectal Dis. 2007 Jun;22(6):661-6. doi: 10.1007/s00384-006-0224-4. Epub 2006 Nov 9.
DNA methylation plays an important role during colorectal cancer (CRC) carcinogenesis. DNA methyltransferase 1 (DNMT1) is responsible for maintaining DNA methylation. We addressed the significance of DNMT1 expression in CRC.
We measured the expression of DNMT1 in CRC tissues and in their corresponding distal normal colorectal mucosa using reverse transcriptase-polymerase chain reaction and immunohistochemical analysis.
The mean +/- SD of DNMT1 mRNA in CRC tissues was 1.04 +/- 0.36, which was significantly higher than that in their corresponding distal normal colorectal mucosa (0.58 +/- 0.44, P < 0.05). Fifty-eight out of 77 (75.3%) CRC tissues and only 30 out of 77 (39%) corresponding distant normal colorectal mucosa showed immunoreactivity (P < 0.001). We also found that the immunoreactivity of DNMT1 was higher in mucosa adjacent to cancer than in corresponding normal colorectal mucosa; high immunoreactivity was significantly correlated with poor differentiation in CRC tissues (P = 0.008). No significant associations were found between DNMT1 immunoreactivity and the following variables: age, sex, locations of cancer, Duke's phase, and the presence of lymph-node metastasis.
These findings suggested that DNMT1 was associated with the malignant phenotype, and dysregulation of DNMT1 expression was present in tumor cells of CRC.
DNA甲基化在结直肠癌(CRC)致癌过程中起重要作用。DNA甲基转移酶1(DNMT1)负责维持DNA甲基化。我们探讨了DNMT1在结直肠癌中的表达意义。
我们使用逆转录聚合酶链反应和免疫组织化学分析方法,检测了DNMT1在结直肠癌组织及其相应的远端正常结直肠黏膜中的表达。
结直肠癌组织中DNMT1 mRNA的平均值±标准差为1.04±0.36,显著高于其相应的远端正常结直肠黏膜(0.58±0.44,P<0.05)。77例结直肠癌组织中有58例(75.3%)显示免疫反应性,而77例相应的远端正常结直肠黏膜中只有30例(39%)显示免疫反应性(P<0.001)。我们还发现,癌旁黏膜中DNMT1的免疫反应性高于相应的正常结直肠黏膜;高免疫反应性与结直肠癌组织中的低分化显著相关(P=0.008)。在DNMT1免疫反应性与以下变量之间未发现显著关联:年龄、性别、癌症位置、杜克分期和淋巴结转移情况。
这些发现表明DNMT1与恶性表型相关,且结直肠癌肿瘤细胞中存在DNMT1表达失调。