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甲基化在乳腺癌中对凋亡基因APAF1、DAPK1和BCL2调控中的作用

Role of Methylation in the Regulation of Apoptosis Genes APAF1, DAPK1, and BCL2 in Breast Cancer.

作者信息

Loginov V I, Pronina I V, Burdennyi A M, Pereyaslova E A, Braga E A, Kazubskaya T P, Kushlinskii N E

机构信息

Research Institute of Pathology and Pathophysiology, Moscow, Russia.

Medical Genetic Research Center, Moscow, Russia.

出版信息

Bull Exp Biol Med. 2017 Apr;162(6):797-800. doi: 10.1007/s10517-017-3716-z. Epub 2017 Apr 21.

Abstract

Changes in the levels of expression of proapoptotic genes APAF1 and DAPK1 and antiapoptotic gene BCL2 were studied by real time PCR in specimens of tumors and histologically intact tissue from 28 patients with breast cancer. The expression of APAF1 and DAPK1 was below the normal in the majority of tumor samples (p<0.05), while the level of BCL2 mRNA more often surpassed the normal (p<0.1). Study of the same sample of specimens by methylspecific PCR showed predominance of APAF1 and DAPK1 hypermethylation (p<0.05 and p<0.1, respectively) and more frequent hypomethylation of BCL2. A significant correlation between changes in the levels of expression and methylation (r=0.40-0.49; p<0.05) was detected for all three genes (APAF1, DAPK1, and BCL2). The results suggest that methylation play an important role in the regulation of these apoptosis system genes in breast cancer.

摘要

通过实时PCR研究了28例乳腺癌患者肿瘤标本及组织学正常组织中促凋亡基因APAF1和DAPK1以及抗凋亡基因BCL2的表达水平变化。大多数肿瘤样本中APAF1和DAPK1的表达低于正常水平(p<0.05),而BCL2 mRNA水平则更常超过正常水平(p<0.1)。通过甲基特异性PCR对相同样本进行研究发现,APAF1和DAPK1存在高甲基化优势(分别为p<0.05和p<0.1),而BCL2则更常出现低甲基化。检测到所有三个基因(APAF1、DAPK1和BCL2)的表达水平变化与甲基化之间存在显著相关性(r=0.40-0.49;p<0.05)。结果表明,甲基化在乳腺癌这些凋亡系统基因的调控中起重要作用。

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