MAGE-A9 和 MAGE-A11 在乳腺癌中的表达及其表达机制。

Expressions of MAGE-A9 and MAGE-A11 in breast cancer and their expression mechanism.

机构信息

Department of Oncology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China; Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China.

Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China.

出版信息

Arch Med Res. 2014 Jan;45(1):44-51. doi: 10.1016/j.arcmed.2013.10.005. Epub 2013 Dec 5.

DOI:10.1016/j.arcmed.2013.10.005

PMID:24316396

Abstract

BACKGROUND AND AIMS

The MAGE gene encodes cancer/testis antigens that are selectively expressed in various types of human neoplasms but not in normal tissues other than testis and placenta. However, the expression pattern of MAGE-A9 and MAGE-A11 in breast cancer patients is still unclear. The purpose of our study is to investigate the expression pattern and mechanism of MAGE-A9 and MAGE-A11 in breast cancer patients.

METHODS

The expression of MAGE-A9 and MAGE-A11 was investigated in 60 breast benign diseases specimens, 60 tumor-free breast specimens and 60 breast cancer specimens by RT-PCR, and their correlation with clinicopathological parameters was elucidated. We examined the influence of the DNA methylase inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR) together with the histone deacetylase inhibitor trichostatin A (TSA) on the expression of MAGE-A9 and MAGE-A11 genes in two breast cancer cell lines.

RESULTS

The expression rates of MAGE-A9 and MAGE-A11 in breast cancer specimens were 45 and 66.7%, respectively. MAGE-A9 and MAGE-A11 expression was positively associated with estrogen-receptor (ER) and HER-2 expression (p <0.05). 5-Aza-CdR treatment alone could induce the expression of MAGE-A9 and MAGE-A11 in cell lines that did not express this antigen. TSA treatment alone had no influence on MAGE-A9 and MAGE-A11 gene expression. However, TSA was able synergistically to enhance 5-aza-CdR-mediated MAGE-A transcription (p <0.05).

CONCLUSIONS

Our data show that MAGE-A9 and MAGE-A11 are tumor-specific antigens and not only DNA hypermethylation but also histone deacetylation is responsible for the mechanism underlying MAGE-A9 and MAGE-A11 gene silencing.

摘要

背景与目的

MAGE 基因编码的肿瘤/睾丸抗原在多种人类肿瘤中选择性表达，但除睾丸和胎盘外，在正常组织中不表达。然而，MAGE-A9 和 MAGE-A11 在乳腺癌患者中的表达模式尚不清楚。本研究旨在探讨 MAGE-A9 和 MAGE-A11 在乳腺癌患者中的表达模式和机制。

方法

采用 RT-PCR 法检测 60 例乳腺良性疾病标本、60 例无瘤乳腺标本和 60 例乳腺癌标本中 MAGE-A9 和 MAGE-A11 的表达，并探讨其与临床病理参数的关系。我们检测了 DNA 甲基转移酶抑制剂 5-氮杂-2'-脱氧胞苷（5-aza-CdR）联合组蛋白去乙酰化酶抑制剂曲古抑菌素 A（TSA）对两种乳腺癌细胞系中 MAGE-A9 和 MAGE-A11 基因表达的影响。

结果

乳腺癌标本中 MAGE-A9 和 MAGE-A11 的表达率分别为 45%和 66.7%。MAGE-A9 和 MAGE-A11 的表达与雌激素受体（ER）和 HER-2 表达呈正相关（p<0.05）。5-aza-CdR 单独处理可诱导不表达该抗原的细胞系中 MAGE-A9 和 MAGE-A11 的表达。TSA 单独处理对 MAGE-A9 和 MAGE-A11 基因表达无影响。然而，TSA 能够协同增强 5-aza-CdR 介导的 MAGE-A 转录（p<0.05）。