Expression of BORIS in melanoma: lack of association with MAGE-A1 activation

Int J Cancer. 2008 Feb 15;122(4):777-84. doi: 10.1002/ijc.23140.

Abstract

Several genes with specific expression in germ cells show aberrant activation in different types of tumors. These genes, termed cancer-germline (CG) genes, encode tumor-specific antigens, which represent potential targets for therapeutic vaccination against cancer. The germline-specific gene BORIS (Brother Of the Regulator of Imprinted Sites), which encodes an 11-zinc-fingers transcriptional regulator, was recently qualified as a new CG gene, as it was found to be activated in a variety of tumor samples. Moreover, it was suggested that BORIS might be responsible for the activation of most other CG genes, including gene MAGE-A1, in tumors. In the present study, we evaluated the frequency of BORIS activation in melanoma by quantitative RT-PCR. BORIS activation was detected in 27% (n = 63) melanoma tissue samples. Surprisingly, many melanoma samples expressed MAGE-A1 and other CG genes in the absence of BORIS activation, suggesting that BORIS is not an obligate factor for activation of these genes in melanoma. Consistently, forced expression of BORIS in melanoma cell lines did not induce expression of MAGE-A1. Our results indicate that BORIS may serve as a useful target for immunotherapy of melanoma. However, it appears that BORIS is neither necessary nor sufficient for the activation of other CG genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • Azacitidine
  • Blotting, Western
  • CpG Islands
  • DNA Methylation
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Melanoma / genetics*
  • Melanoma / metabolism
  • Melanoma / pathology
  • Melanoma-Specific Antigens
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Retroviridae / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Antigens, Neoplasm
  • CTCFL protein, human
  • DNA-Binding Proteins
  • MAGEA1 protein, human
  • Melanoma-Specific Antigens
  • Neoplasm Proteins
  • RNA, Messenger
  • Azacitidine