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在中国散发性女性乳腺癌发生过程中 14-3-3σ 的异常甲基化谱及其转录/表达水平降低。

Aberrant methylation profile of 14-3-3 sigma and its reduced transcription/expression levels in Chinese sporadic female breast carcinogenesis.

机构信息

The Neurosurgery Department, Taihe Hospital, Yunyang Medicinal College, Shiyan, Hubei, 442000, China.

出版信息

Med Oncol. 2010 Sep;27(3):791-7. doi: 10.1007/s12032-009-9287-8. Epub 2009 Aug 14.

Abstract

To study the relation of 14-3-3 sigma gene promoter hypermethylation and its transcription expression levels in sporadic breast carcinogenesis. Methylation of 14-3-3 sigma gene was detected by sensitive MSP assay in carcinous, non-cancerous, and normal tissue, and its mRNA was also detected by real time PCR based on SYBR Green 1 as well, and protein was detected by west blotting assay. The methylation frequencies of 14-3-3 sigma were 90% in 68 cases of sporadic breast cancer patients. Methylation was presented in portions (2/13, 18%) of hyperplastic samples, and no hypermethylation was presented in normal tissue. The methylation change of 14-3-3 sigma gene was markedly related with various types, grades, and lymph node metastases (P < 0.05), and no significant differences in methylation frequencies were seen between premenopause and postmenopause (P > 0.05). The methylation of 14-3-3 sigma shows reverse relation with its mRNA transcription and expression level (P < 0.05). Only was lymph node metastases strongly associated with poor outcome (P = 0.02). Whether 14-3-3 sigma promoter methylation or not did not affect the 5 years survival rate of sporadic breast cancer patients (P > 0.05). Epigenetics alterations of the 14-3-3 sigma can contribute to reducing or losing expression of 14-3-3 sigma protein, which play an important role in the development of sporadic breast carcinomas and involved in various types, grades, and lymph node metastases. Otherwise, node metastases of breast carcinogenesis patients are strongly associated with poor outcome.

摘要

研究散发性乳腺癌发生中 14-3-3σ 基因启动子超甲基化与其转录表达水平的关系。采用敏感 MSP 法检测癌组织、癌旁组织和正常组织中 14-3-3σ 基因甲基化,实时荧光定量 PCR 检测其 mRNA 表达,Western blot 检测其蛋白表达。结果 68 例散发性乳腺癌患者中,14-3-3σ 基因甲基化频率为 90%,增生性病变中存在部分甲基化(2/13,18%),而正常组织中未见甲基化。14-3-3σ 基因甲基化改变与肿瘤的类型、分级、淋巴结转移显著相关(P<0.05),与患者的绝经状态无关(P>0.05)。14-3-3σ 基因甲基化与其 mRNA 转录和蛋白表达水平呈负相关(P<0.05)。仅淋巴结转移与不良预后显著相关(P=0.02)。14-3-3σ 基因启动子甲基化与否不影响散发性乳腺癌患者的 5 年生存率(P>0.05)。14-3-3σ 的表观遗传学改变可能导致其蛋白表达降低或缺失,在散发性乳腺癌的发生、发展中起重要作用,并与肿瘤的类型、分级和淋巴结转移相关。而淋巴结转移是影响乳腺癌患者预后的重要因素。

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