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Potential role of 5-aza-2'-deoxycytidine induced MAGE-A4 expression in immunotherapy for anaplastic thyroid cancer.
- Source :
-
Surgery [Surgery] 2013 Dec; Vol. 154 (6), pp. 1456-62; discussion 1462. - Publication Year :
- 2013
-
Abstract
- Background: Melanoma antigen gene family (MAGE)-A4, a member of the cancer testis antigen family, has been reported in various cancers including melanoma, bladder, head and neck, oral, and lung, and is a potential target for T-cell-receptor-based immunotherapy. Baseline expression levels of the MAGE-A4 gene in thyroid cancer cell lines have not been previously studied thoroughly.<br />Methods: Human thyroid cancer cell lines (8505c, HTh7, BCPAP, and TPC-1) were treated with either 10 μmol/L 5'-azacytidine (Aza) or 10 μmol/L 5-AZA-2'deoxycytidine (DAC) and evaluated for various MAGEA gene expression. Later melanoma cell lines A375 and 8505c were treated with PLX4720 in combination with DAC and evaluated for MAGE-A4 expression.<br />Results: Only BCPAP cells expressed moderate levels of MAGE-A3 and MAGE-A6 at baseline. Treatment with DAC/Aza induced the expression of MAGE-A4 and MAGE-A1 in 8505c cells. PLX4720 treatment did not affect MAGE-A4 expression in 8505c cells, but increased its expression in A375 cells. In contrast, addition of PLX4720 to DAC-treated 8505c cells decreased the previously induced MAGE-A4 expression by DAC in these cells. A similar decrease in MAGE-A4 expression by DAC was also seen in 8505cBRAF(-/-) cells. Although DAC treatment resulted in demethylation of the MAGE-A4 promoter in 2 CpG sites, PLX addition to DAC did not affect the demethylation status.<br />Conclusion: Demethylating agents increased the expression of MAGE genes in thyroid cancer cells. The effect of BRAFV600E inhibitors on MAGE-A4 expression suggest the role of downstream MEK/BRAF signaling in its expression apart from promoter demethylation being the sole requirement. Expression of MAGE-A4 may make immunotherapeutic intervention possible in selected patients with thyroid cancer.<br /> (Copyright © 2013 Mosby, Inc. All rights reserved.)
- Subjects :
- Azacitidine pharmacology
Cell Line, Tumor
CpG Islands
DNA Methylation drug effects
DNA Methylation genetics
Decitabine
Gene Expression drug effects
Humans
Indoles pharmacology
MAP Kinase Signaling System drug effects
Melanoma genetics
Melanoma immunology
Melanoma therapy
Promoter Regions, Genetic drug effects
Proto-Oncogene Proteins B-raf antagonists & inhibitors
Proto-Oncogene Proteins B-raf genetics
Proto-Oncogene Proteins B-raf metabolism
Sulfonamides pharmacology
Thyroid Carcinoma, Anaplastic
Thyroid Neoplasms genetics
Thyroid Neoplasms immunology
Antigens, Neoplasm genetics
Azacitidine analogs & derivatives
Immunotherapy methods
Neoplasm Proteins genetics
Thyroid Neoplasms therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1532-7361
- Volume :
- 154
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Surgery
- Publication Type :
- Academic Journal
- Accession number :
- 24238058
- Full Text :
- https://doi.org/10.1016/j.surg.2013.07.009