Expressions of MAGE-A9 and MAGE-A11 in Breast Cancer and their Expression Mechanism

Abstract

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. 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. 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). 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.