Reduced metastasis-suppressor gene mRNA-expression in breast cancer brain metastases

J Cancer Res Clin Oncol. 2005 Mar;131(3):191-8. doi: 10.1007/s00432-004-0629-9. Epub 2004 Dec 8.


Purpose: Brain metastases are an increasingly common complication in breast cancer patients. The Metastasis Suppressor Genes (MSG) Nm23, KISS1, KAI1, BRMS1, and Mkk4 have been associated with the metastatic potential of breast cancer in vitro and in vivo.

Methods: The mRNA expression of Nm23, KISS1, KAI1, BRMS1, and Mkk4 in fresh frozen tissue samples of brain metastases from ductal invasive breast cancer specimens was examined in relation to primary tumors. In a first step, mRNA expression screening was carried out using a semi-quantitative RT-PCR approach, in a second step quantitative real-time RT-PCR was performed on selected specimens. By immunohistochemical staining, gene products were visualized on the protein level.

Results: Semi-quantitative RT-PCR revealed reduced mRNA expression of Nm23, KISS1, KAI1, BRMS, and Mkk4 in brain metastases. Results for KISS1, KAI1, BRMS, and Mkk4 were confirmed by real-time RT-PCR. In detail, mRNA expression reduction in breast cancer brain metastases was tenfold. Expression of MSG could be confirmed by immunohistochemical staining on protein level.

Conclusions: Our investigations revealed significantly reduced mRNA expression of metastases suppressor genes KISS1, KAI1, BRMS1, and Mkk4 in breast cancer brain metastasis. Particularly, in the case of KISS1 and Mkk4, an important role for future treatment of patients with breast cancer brain metastatic lesions can be assumed.

MeSH terms

  • Antigens, CD / analysis
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • Brain Neoplasms / chemistry*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / secondary
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, Tumor Suppressor
  • Humans
  • Immunohistochemistry
  • Kangai-1 Protein
  • Kisspeptins
  • MAP Kinase Kinase 4 / analysis
  • Membrane Glycoproteins / analysis
  • NM23 Nucleoside Diphosphate Kinases
  • Neoplasm Proteins / analysis
  • Nucleoside-Diphosphate Kinase / analysis
  • Proteins / analysis
  • Proto-Oncogene Proteins / analysis
  • RNA, Messenger / analysis
  • Repressor Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Suppressor Proteins / analysis*
  • Tumor Suppressor Proteins / genetics


  • Antigens, CD
  • BRMS1 protein, human
  • Biomarkers, Tumor
  • CD82 protein, human
  • KISS1 protein, human
  • Kangai-1 Protein
  • Kisspeptins
  • Membrane Glycoproteins
  • NM23 Nucleoside Diphosphate Kinases
  • Neoplasm Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Repressor Proteins
  • Tumor Suppressor Proteins
  • MAP Kinase Kinase 4
  • NME1 protein, human
  • Nucleoside-Diphosphate Kinase