Regulation of high molecular weight-melanoma associated antigen (HMW-MAA) gene expression by promoter DNA methylation in human melanoma cells

W. Luo, X. Wang, T. Kageshita, S. Wakasugi, A. R. Karpf, S. Ferrone

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

The human high molecular weight-melanoma associated antigen (HMW-MAA) is a membrane-bound chondroitin sulfate proteoglycan that is variably expressed in a high percentage of melanoma cell lines and tumors. Since the mechanism(s) regulating HMW-MAA expression has(ve) not been defined, in this study, we have examined whether promoter DNA methylation regulates the level of HMW-MAA expression. In melanoma cell lines, the level of HMW-MAA mRNA and protein expression is coordinately regulated, implicating a transcriptional control mechanism. Consistent with a role for regulation by DNA methylation, we have found that a dense CpG island flanks the human HMW-MAA gene transcriptional start site. Methylation-specific PCR and sodium bisulfite DNA sequencing analyses indicate that the HMW-MAA promoter is heavily methylated in melanoma cell lines, melanoma lesions and normal lymphocytes that do not express HMW-MAA; in contrast, the HMW-MAA promoter is not methylated in melanoma cell lines and tumors that express this antigen. In addition, HMW-MAA expression is markedly induced in HMW-MAA-negative melanoma cell lines by incubation with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine. In summary, our results establish DNA methylation as a key regulator of HMW-MAA expression by human melanoma cells. This information represents a useful background to optimize immunotherapeutic strategies targeting HMW-MAA.

Original languageEnglish (US)
Pages (from-to)2873-2884
Number of pages12
JournalOncogene
Volume25
Issue number20
DOIs
StatePublished - May 11 2006
Externally publishedYes

Keywords

  • 5-aza 2′-deoxycytidine
  • HMW-MAA expression
  • Melanoma cell lines and lesions
  • Promoter DNA methylation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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