MAGE-D4B is a novel marker of poor prognosis and potential therapeutic target involved in breast cancer tumorigenesis

Int J Cancer. 2012 May 1;130(9):1991-2002. doi: 10.1002/ijc.26200. Epub 2011 Aug 8.

Abstract

Melanoma-associated antigen (MAGE) family members are generally described as tumor-specific antigens. An association between MAGE-D4B and breast cancer has yet to be reported and the functional role of the encoded protein has never been established. We performed microarray analysis of 104 invasive breast tumors and matched non-cancerous breast biopsies. qPCR was used for validation in an independent biobank. To investigate the biological relevance of MAGE-D4B in breast tumorigenesis, its phenotypic effects were assessed in vitro. Overall, MAGE-D4B was detected in 43% of tumors while undetected in normal breast tissue. MAGE-D4B was found to correlate with tumor progression and to be an independent prognostic marker for poor outcome in term of relapse-free and overall survival, with potential predictive relevance in relation to response to chemotherapy. RNA interference-mediated knockdown of MAGE-D4B significantly hampered the invasive properties of Hs578T cells by affecting anchorage-independent growth, adhesion, migration and invasion affecting anchorage-independent growth, adhesion, migration and invasion and by modulating expression of invasion-suppressor gene E-cadherin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Movement
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Neoplasm Staging
  • Oligonucleotide Array Sequence Analysis / methods
  • Prognosis
  • Treatment Outcome

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Cadherins
  • MAGED1 protein, human
  • Neoplasm Proteins