Promoter Demethylation and Histone Acetylation Mediate Gene Expression of <i>MAGE-A1, -A2, -A3</i>, and <i>-A12</i> in Human Cancer Cells

Wischnewski, Frank; Pantel, Klaus; Schwarzenbach, Heidi

doi:10.1158/1541-7786.mcr-05-0229

Cited by 161 publications

(143 citation statements)

References 34 publications

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“…No difference in overall survival was found, but the median follow-up of these patients' series was too short to conclude that point. This is in agreement with recent findings in other cancers showing that CT-X gene expression is often coordinated due to hypomethylation of their promoters (50,51). In addition, CT-X gene expression in patients with epithelial cancers is often associated with a poor patient outcome (52)(53)(54).…”

Section: Discussionsupporting

confidence: 92%

Cancer/Testis Genes in Multiple Myeloma: Expression Patterns and Prognosis Value Determined by Microarray Analysis

Condomines

Hose

Raynaud

et al. 2007

The Journal of Immunology

109

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Cancer-testis (CT) Ags are expressed in testis and malignant tumors but rarely in nongametogenic tissues. Due to this pattern, they represent attractive targets for cancer vaccination approaches. The aims of the present study are: 1) to assess the expression of CT genes on a pangenomic base in multiple myeloma (MM); 2) to assess the prognosis value of CT gene expression; and 3) to provide selection strategies for CT Ags in clinical vaccination trials. We report the expression pattern of CT genes in purified MM cells (MMC) of 64 patients with newly diagnosed MM and12 patients with monoclonal gammopathy of unknown significance, in normal plasma cell and B cell samples, and in 20 MMC lines. Of the 46 CT genes interrogated by the Affymetrix HG-U133 set arrays, 35 are expressed in the MMC of at least one patient. Of these, 25 are located on chromosome X. The expression of six CT genes is associated with a shorter event-free survival. The MMC of 98% of the patients express at least one CT gene, 86% at least two, and 70% at least three CT genes. By using a set of 10 CT genes including KM-HN-1, MAGE-C1, MAGE-A3/6/12, MAGE-A5, MORC, DDX43, SPACA3, SSX-4, GAGE-1–8, and MAGE-C2, a combination of at least three CT genes—desirable for circumventing tumor escape mechanisms—is obtained in the MMC of 67% of the patients. Provided that the immunogenicity of the products of these 10 CT genes is confirmed, gene expression profiling could be useful in identifying which CT Ags could be used to vaccinate a given patient.

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Section: Discussionsupporting

confidence: 92%

Cancer/Testis Genes in Multiple Myeloma: Expression Patterns and Prognosis Value Determined by Microarray Analysis

Condomines

Hose

Raynaud

et al. 2007

The Journal of Immunology

109

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“…Recent studies (Weber et al, 1994;Sigalotti et al, 2004;Wischnewski et al, 2006) have shown that epigenetic manipulation could enhance TAA expression including MAGE family, which is based on these TAA genes commonly with hypermethylated CpG sites in promoter region. Here, we report at the first time the methylation status of MAGED4.…”

Section: Discussionmentioning

confidence: 99%

“…MAGE is a large gene family, in which some genes encode tumor-associated antigens with characteristics of broad expression in various tumors but restricted in normal tissues, and recognizing by cytotoxic T lymphocytes (CTLs) (Inoue et al, 1995;Wischnewski et al, 2006). Some of MAGE antigens and their epitope peptides constitute important targets for antitumor immunotherapy with a number of clinical studies already completed or underway (Duffour et al, 1999;Rosenberg et al, 2004;Morse et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…Although a presumptive CpG island of MAGED4 around the transcriptional site has been reported , its methylation status is not yet known so far. Generally, most MAGE family genes present CpG island in the promoter region, and demethylation of this site is related to induce expression of some genes in this family (Weber et al, 1994;Serrano et al, 1996;Wischnewski et al, 2006). This implies that MAGED4 could be an DNA methylation-mediated regulation gene.…”

Section: Introductionmentioning

confidence: 99%

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MAGED4 Expression in Glioma and Upregulation in Glioma Cell Lines with 5-Aza-2'-Deoxycytidine Treatment

Zhang¹,

Shen²,

Xie³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Melanoma-associated antigen (MAGE) family genes have been considered as potentially promising targets for anticancer immunotherapy. MAGED4 was originally identified as a glioma-specific antigen. Current knowledge about MAGED4 expression in glioma is only based on mRNA analysis and MAGED4 protein expression has not been elucidated. In the present study, we investigated this point and found that MAGED4 mRNA and protein were absent or very lowly expressed in various normal tissues and glioma cell line SHG44, but overexpressed in glioma cell lines A172,U251,U87-MG as well as glioma tissues, with significant heterogeneity. Furthermore, MAGED4 protein expression was positively correlated with the glioma type and grade. We also found that the expression of MAGED4 inversely correlated with the overall methylation status of the MAGED4 promoter CpG island. Furthermore, when SHG44 and A172 with higher methylation were treated with the DNA demethylating agent 5-aza-2'-deoxycytidine (5-AZA-CdR) reactivation of MAGED4 mRNA was mediated by significant demethylation in SHG44 instead of A172. However, 5-AZA-CdR treatment had no effect on MAGED4 protein in both SHG44 and A172 cells. In conclusion, MAGED4 is frequently and highly expressed in glioma and is partly regulated by DNA methylation. The results suggest that MAGED4 might be a promising target for glioma immunotherapy combined with 5-AZA-CdR to enhance its expression and eliminate intratumor heterogeneity.

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“…Expression of several CTA has been linked to DNA hypomethylation [15,20,21]. We, therefore, investigated whether epigenetic treatment might increase the comparably infrequent CTA expression in AML cells.…”

Section: Demethylation But Not Inhibition Of Histone Deacetylation Inmentioning

confidence: 99%

Cancer‐testis antigen expression and its epigenetic modulation in acute myeloid leukemia

et al. 2011

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Cancer-testis antigens (CTA) represent attractive targets for tumor immunotherapy. However, a broad picture of CTA expression in acute myeloid leukemia (AML) is missing. CTA expression was analyzed in normal bone marrow (BM) as well as in AML cell lines before and after treatment with demethylating agents and/or histone acetylase inhibitors. Presence of selected CTA with a strictly tumor-restricted expression was then determined in samples of patients with AML before and after demethylating therapy. Screening AML cell lines for the expression of 20 CTA, we identified six genes (MAGE-A3, PRAME, ROPN1, SCP-1, SLLP1, and SPO11) with an AML-restricted expression. Analyzing the expression of these CTA in blast-containing samples from AML patients (N 5 64), we found all samples to be negative for MAGE-A3 and SPO11 while a minority of patients expressed ROPN1 (1.6%), SCP-1 (3.1%), or SLLP1 (9.4%). The only CTA expressed in substantial proportion of patients (53.1%) was PRAME. Following demethylating treatment with 5 0 -aza-2 0 -deoxycytidine, we observed an increased or de novo expression of CTA, in particular of SSX-2, in AML cell lines. In AML patients, we detected increased expression of PRAME and induction of SSX-2 after demethylating therapy with 5-azacytidine. With the exception of PRAME, CTA are mostly absent from AML blasts. However, demethylating treatment induces strong expression of CTA, particularly of SSX-2, in vitro and in vivo. Therefore, we propose that CTA-specific immunotherapy for AML should preferentially target PRAME and/or should be combined with the application of demethylating agents opening the perspective for alternative targets like CTA SSX-2. Am. J. Hematol. 86:918-922, 2011. V

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Promoter Demethylation and Histone Acetylation Mediate Gene Expression of MAGE-A1, -A2, -A3, and -A12 in Human Cancer Cells

Cited by 161 publications

References 34 publications

Cancer/Testis Genes in Multiple Myeloma: Expression Patterns and Prognosis Value Determined by Microarray Analysis

Cancer/Testis Genes in Multiple Myeloma: Expression Patterns and Prognosis Value Determined by Microarray Analysis

MAGED4 Expression in Glioma and Upregulation in Glioma Cell Lines with 5-Aza-2'-Deoxycytidine Treatment

Cancer‐testis antigen expression and its epigenetic modulation in acute myeloid leukemia

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