gms | German Medical Science

55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

25. bis 28.04.2004, Köln

cDNA profiling of breast cancer brain and bone metastases in vitro

cDNA Profil von Mammakarzinom-Hirn- und Knochenmetastasen in-vitro

Meeting Abstract

  • corresponding author Andreas M. Stark - Klinik für Neurochirurgie im Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel
  • D. Palmieri - National Cancer Institute, NIH, Bethesda /USA
  • P. S. Meltzer - National Human Genome Research Institute, NIH, Bethesda /USA
  • H. M. Mehdorn - Klinik für Neurochirurgie im Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel
  • P. S. Steeg - National Cancer Institute, NIH, Bethesda /USA
  • J. Held-Feindt - Klinik für Neurochirurgie im Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel

Deutsche Gesellschaft für Neurochirurgie. Ungarische Gesellschaft für Neurochirurgie. 55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie. Köln, 25.-28.04.2004. Düsseldorf, Köln: German Medical Science; 2004. DocMO.04.09

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2004/04dgnc0052.shtml

Veröffentlicht: 23. April 2004

© 2004 Stark et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective

Haematogenous metastasis to the bone and brain is an increasingly common complication in cancer. Recently, bone (231-bone) and brain- (231-brain) seeking clones of MDA-MB-231 (231-parental) breast cancer cells have been established in a mouse model. We performed cDNA expression analysis of the different sublines to identify factors related to the metastatic spread to brain and bone.

Methods

Total RNA was isolated from MDA-MB-231 cells (parental) and the two sublines using the Trizol®-method. Reverse transcription labelling was performed with fluorescence markers (Cy5-dUTP and Cy3-dUTP) and followed by hybridization to the 16K gene chip fabricated by the National Human Genome Research Institute, NIH, Bethesda, MD, USA. Hybridizations were performed for (1) 231-parental versus 231-bone as well as (2) 231-parental versus 231-brain cells. For data analysis, a threshold value of 2.5 fold over or under expression was defined to identify significant changes in gene expression. cDNA array results were validated using semiquantative RT-PCR.

Results

113 genes were significantly over- or underexpressed in brain and / or bone-seeking 231-variants in comparison to 231-parental cells. Among these, 10 genes were selected for semi-quantative RT-PCR validation. Finally, three candidate metastasis regulatory genes were identified: (1) metastasis suppressor gene KiSS-1, (2) the tyrosine kinase transmembrane receptor TIE-1 which is supposed to be essential for vascular genesis and (3) PTPRN2, a protein that is associated with CNS and pancreas genesis. Functional experiments further characterized the factors identified.

Conclusions

Gene chips offer expression profiling of cells and tissue specimens on a genome-wide scale. Using the 16K gene chip of the NHGRI, we identified over 100 potential metastasis regulatory genes. RT-PCR data validation identified 3 "hot spot" metastasis regulatory genes, which have to be further examined for their role in breast cancer brain and bone metastases.