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Clinical Research
Expression of melanoma antigen genes in human breast cancer: Association with major demographic and pathophysiologic variables and effect of drug treatment
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Abstract:
Objective: The purpose of our study was to analyze the expression of melanoma antigen genes MAGE-A9 and MAGE-A11 in benign and malignant breast cancer specimens and in breast cancer cell lines following drug treatment. Methods: Tissue specimens were obtained from tumor-free breast (n=60), benign breast cancer (n=60) and malignant breast cancer (n=60), respectively. The mRNA abundance and protein content of MAGE-A9 and MAGE-A11 in these specimens were determined by RT-PCR and immunohistochemistry respectively and were analyzed for their associations with the major demographic, physiologic and pathologic variables. To examine the influence of chemotherapeutic drugs on MAGEs in breast cancer, MCF-7 and MDA-MB-231 cells were treated with 5-Aza-2’-deoxycytidine (5-Aza-CdR), a DNA methylase inhibitor, and trichostatin A (TSA), a histone deacetylase inhibitor, either each alone or both together, and mRNA levels of MAGE-A9 and MAGE-A11 were assessed by RT-PCR. Results：MAGE-A9 and MAGE-A11 transcripts were detected in 45% and 66.7% of breast cancer specimens respectively and MAGE-A9 and MAGE-A11 proteins in 433% and 63.3% of cancer specimens, respectively. MAGE-A9 and MAGE-A11 expression was positively correlated with the expression of estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER-2) in cancer specimens (P<0.05). Neither transcripts nor proteins of MAGE-A9 and MAGE-A11 were detected in normal control specimens. While 5-Aza-CdR alone induced the expression of MAGE-A9 and MAGE-A11 in the test cell lines, TSA alone showed no effects. However, TSA was able to enhance 5-Aza-CdR-induced MAGE-A transcription (P<0.01).Conclusion：MAGE-A9 and MAGE-A11 are tumor-specific antigens. Both DNA hypermethylation and histone deacetylation are possible mechanisms underlying MAGE-A9 and MAGE-A11 gene silencing.
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Project Supported:
Project supported by the Natural Science Foundation of Hebei Province（No.H2012206077）
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