Expression of the MAGE-1 tumor antigen is up-regulated by the demethylating agent 5-Aza-2′-deoxycytidine

J. Weber, M. Salgaller, D. Samid, B. Johnson, M. Herlyn, N. Lassam, J. Treisman, S. A. Rosenberg

Research output: Contribution to journalArticle

Abstract

MAGE-1 is a gene that encodes an antigen on a melanoma cell line that is recognized by cytolytic T-cells. We have used a reverse transcriptionpolymerase chain reaction assay to analyze expression of the MAGE-1 gene by cell lines from different types of tumors, melanomas from different stages of disease progression, normal diploid cell lines, and melanocyte and nevus tissue from which malignant melanomas are derived. MAGE-1 is expressed by melanoma tissue from all stages of disease, but not melanocytes, nevus tissue, or any normal diploid cell line tested. A fraction of tumor lines derived from various epithelial and neuroectodermal malignancies expressed MAGE-1 but not peripheral blood cells from patients with melanoma. 5-Aza-2′-deoxycytidine (DAC), a demethylating agent, was capable of inducing MAGE-1 expression by a MAGE-1-negative melanoma cell line 888-mel as well as by a number of other melanoma cell lines. At an optimum concentration of 1 μM DAC, MAGE-1 expression was detectable by 24 h, plateaued by 72 h, but remained high for two weeks after removal of DAC from treated 888-mel cells, consistent with induction by demethylation. With the exception of tumor-infiltrating leukocytes, no normal diploid cell line could be induced with DAC to upregulate MAGE-1 expression. DAC-treated 888-mel cells were lysed by a MAGE-1-specific major histocompatibility complex restricted cytolytic T-cell clone, whereas control untreated cells were not, suggesting that production of the antigen encoded by the MAGE-1 gene was induced by DAC and that it was presented in association with major histocompatibility complex class I molecules at the cell surface for T-cell recognition.

Original languageEnglish (US)
Pages (from-to)1766-1771
Number of pages6
JournalCancer Research
Volume54
Issue number7
StatePublished - Apr 1 1994
Externally publishedYes

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decitabine
Neoplasm Antigens
Melanoma
Cell Line
Diploidy
Nevus
Melanocytes
Major Histocompatibility Complex
T-Lymphocytes
Genes
Antigens
Neoplasms
Tumor Cell Line
Disease Progression
Blood Cells
Leukocytes
Up-Regulation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Weber, J., Salgaller, M., Samid, D., Johnson, B., Herlyn, M., Lassam, N., ... Rosenberg, S. A. (1994). Expression of the MAGE-1 tumor antigen is up-regulated by the demethylating agent 5-Aza-2′-deoxycytidine. Cancer Research, 54(7), 1766-1771.

Expression of the MAGE-1 tumor antigen is up-regulated by the demethylating agent 5-Aza-2′-deoxycytidine. / Weber, J.; Salgaller, M.; Samid, D.; Johnson, B.; Herlyn, M.; Lassam, N.; Treisman, J.; Rosenberg, S. A.

In: Cancer Research, Vol. 54, No. 7, 01.04.1994, p. 1766-1771.

Research output: Contribution to journalArticle

Weber, J, Salgaller, M, Samid, D, Johnson, B, Herlyn, M, Lassam, N, Treisman, J & Rosenberg, SA 1994, 'Expression of the MAGE-1 tumor antigen is up-regulated by the demethylating agent 5-Aza-2′-deoxycytidine', Cancer Research, vol. 54, no. 7, pp. 1766-1771.
Weber J, Salgaller M, Samid D, Johnson B, Herlyn M, Lassam N et al. Expression of the MAGE-1 tumor antigen is up-regulated by the demethylating agent 5-Aza-2′-deoxycytidine. Cancer Research. 1994 Apr 1;54(7):1766-1771.
Weber, J. ; Salgaller, M. ; Samid, D. ; Johnson, B. ; Herlyn, M. ; Lassam, N. ; Treisman, J. ; Rosenberg, S. A. / Expression of the MAGE-1 tumor antigen is up-regulated by the demethylating agent 5-Aza-2′-deoxycytidine. In: Cancer Research. 1994 ; Vol. 54, No. 7. pp. 1766-1771.
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abstract = "MAGE-1 is a gene that encodes an antigen on a melanoma cell line that is recognized by cytolytic T-cells. We have used a reverse transcriptionpolymerase chain reaction assay to analyze expression of the MAGE-1 gene by cell lines from different types of tumors, melanomas from different stages of disease progression, normal diploid cell lines, and melanocyte and nevus tissue from which malignant melanomas are derived. MAGE-1 is expressed by melanoma tissue from all stages of disease, but not melanocytes, nevus tissue, or any normal diploid cell line tested. A fraction of tumor lines derived from various epithelial and neuroectodermal malignancies expressed MAGE-1 but not peripheral blood cells from patients with melanoma. 5-Aza-2′-deoxycytidine (DAC), a demethylating agent, was capable of inducing MAGE-1 expression by a MAGE-1-negative melanoma cell line 888-mel as well as by a number of other melanoma cell lines. At an optimum concentration of 1 μM DAC, MAGE-1 expression was detectable by 24 h, plateaued by 72 h, but remained high for two weeks after removal of DAC from treated 888-mel cells, consistent with induction by demethylation. With the exception of tumor-infiltrating leukocytes, no normal diploid cell line could be induced with DAC to upregulate MAGE-1 expression. DAC-treated 888-mel cells were lysed by a MAGE-1-specific major histocompatibility complex restricted cytolytic T-cell clone, whereas control untreated cells were not, suggesting that production of the antigen encoded by the MAGE-1 gene was induced by DAC and that it was presented in association with major histocompatibility complex class I molecules at the cell surface for T-cell recognition.",
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