期刊文献+

多发性骨髓瘤患者p16基因甲基化及砷剂诱导去甲基化的研究 被引量:14

Hypermethylation of CpG island of p16 gene and arsenic trioxide induced p16 gene demethylation in multiple myeloma
原文传递
导出
摘要 目的探讨p16基因启动子区CpG岛甲基化在多发性骨髓瘤(MM)患者发病中的作用以及三氧化二砷(As2O3)诱导p16基因的去甲基化作用。方法采用巢式甲基特异性PCR法检测MM患者以及利用As2O3作用前后人MM细胞株U266的p16基因的甲基化状态,RTPCR检测U266细胞用药前后p16基因mRNA的表达变化,生长曲线、MTT法检测As2O3对细胞的生长和增殖抑制。利用流式细胞仪检测DNA含量分析法探讨As2O3对骨髓瘤细胞系U266周期的影响。结果MM患者p16基因的甲基化比例为54.8%,U266细胞存在p16基因甲基化,p16基因不表达,As2O3作用后p16基因甲基化程度明显减弱至消失,与未处理组相比,不同剂量作用72h后p16基因表达阳性条带灰度值与βactin比值分别为0.22±0.10、0.59±0.11、0.68±0.09,阳性对照灰度比值为0.77±0.13,其差异有统计学意义(P<0.01)。结论p16基因甲基化在MM患者中较为常见,这可能为MM的诊断和治疗提供借鉴;As2O3可诱导p16基因去甲基化,使p16基因表达上调,恢复其活性,为去甲基化治疗提供新思路。 Objective To investigate the role of hypemethylation of p16 gene in the pathogenesis of multiple myeloma(MM) and the effect of arsenic trioxide(As_2O_3) induced p16 gene demethylation.Methods Methylation status of p16 gene in MM and U266 cell line exposed to As_2O_3 were detected the nested-methylation specific PCR.The expression of p16 gene mRNA was determined with RT-PCR. The induced growth inhibition of U266 cell by growth curve and MTT and the DNA content of U266 cell were analyzed with flow cytometry after exposure to As_2O_3.Results Hypermethylation of CpG island of p16 gene was observed in 54.8% of the MM patients in our group. p16 gene fail to express in U266 cell line after methylation. As compared with β-actin , the expression of p16 gene mRNA in U266 cell was increased to 0.22±0.10、0.59±0.11、0.68±0.09 after exposure to 0.5 μmol/L、1.0 μmol/L and 2.0 μmol/L As_2O_3 for 72 h.Conclusions These results indicate that methylation of p16 gene is essentioal important in the pathogenesis of MM and may provide a new diagnostic technique and drug target for the treatment of MM. As_2O_3 may activate the expression of p16 gene by demethylation.
出处 《中华内科杂志》 CAS CSCD 北大核心 2005年第6期411-414,共4页 Chinese Journal of Internal Medicine
基金 福建省百千万人才工程基金资助项目(303052801)
关键词 多发性骨髓瘤 P16基因 甲基化 砷剂 诱导作用 去甲基化 MM 细胞生长 Multiple myeloma Methylation Arsenicals
  • 相关文献

参考文献7

  • 1朱新华,陈国强.砷剂对肿瘤的生物学作用[J].国外医学(输血及血液学分册),1998,21(5):314-316. 被引量:17
  • 2Durie BG, Salmon SE. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer, 1975, 36: 842-854.
  • 3Herman JG, Graff JR, Myohanen S, et al. Methylation specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci U S A, 1996,93:9821-9826.
  • 4Palmisano WA, Divine KK, Saccomanno G, et al. Predicting lung cancer by detecting aberrant promoter methylation in sputum. Cancer Res, 2000,60:5954-5958.
  • 5Melki JR, Warnecke P, Vincent PC, et al. Increased DNA methyltranferase expression in leukemia. Leukemia, 1998,12:311-316.
  • 6Baylin SB, Herman JG, Graff JR, et al. Alterations in DNA methylation: a fundamental aspect of neoplasia. Adv Cancer Res, 1998,72:141-196.
  • 7Rein T, DePamphilis ML, Zorbas H. Indentifying 5-methylcytosine and related modifications in DNA genomes. Nucleic Acids Res, 1998,26:2255-2264.

共引文献16

同被引文献160

引证文献14

二级引证文献32

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部