Reduced metastasis-suppressor gene mRNA-expression in breast cancer brain metastases.
OBJECTIVE
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.
Stark
Andreas M
AM
Department of Neurosurgery, University of Schleswig-Holstein Medical Center, Campus Kiel, Schittenhelmstrasse 10, 24105 Kiel, Germany.
Tongers
Kerrin
K
Maass
Nicolai
N
Mehdorn
H Maximilian
HM
Held-Feindt
Janka
J
D015703:Antigens, CD / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001932:Brain Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000556:secondary; D001943:Breast Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D051861:Kangai-1 Protein; D059648:Kisspeptins; D048670:MAP Kinase Kinase 4 / Q000032:analysis; D008562:Membrane Glycoproteins / Q000032:analysis; D054778:NM23 Nucleoside Diphosphate Kinases; D009363:Neoplasm Proteins / Q000032:analysis; D009701:Nucleoside-Diphosphate Kinase / Q000032:analysis; D011506:Proteins / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000032:analysis* / Q000235:genetics
D015703:Antigens, CD; C410024:BRMS1 protein, human; D014408:Biomarkers, Tumor; C497688:CD82 protein, human; C106628:KISS1 protein, human; D051861:Kangai-1 Protein; D059648:Kisspeptins; D008562:Membrane Glycoproteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009363:Neoplasm Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; D048670:MAP Kinase Kinase 4; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase