gms | German Medical Science

61st Annual Meeting of the German Society of Neurosurgery (DGNC) as part of the Neurowoche 2010
Joint Meeting with the Brazilian Society of Neurosurgery on the 20 September 2010

German Society of Neurosurgery (DGNC)

21 - 25 September 2010, Mannheim

Genetic profiling of breast cancer brain metastases: The MDA-MB 231 array experiment

Meeting Abstract

  • Andreas M. Stark - Klinik für Neurochirurgie im Universitätsklinikum Schleswig-Holstein, Campus Kiel, Germany
  • Rolf Mentlein - Institut für Anatomie, Christian-Albrechts-Universität zu Kiel, Germany
  • H. Maximilian Mehdorn - Klinik für Neurochirurgie im Universitätsklinikum Schleswig-Holstein, Campus Kiel, Germany
  • Janka Held-Feindt - Klinik für Neurochirurgie im Universitätsklinikum Schleswig-Holstein, Campus Kiel, Germany

Deutsche Gesellschaft für Neurochirurgie. 61. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC) im Rahmen der Neurowoche 2010. Mannheim, 21.-25.09.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. DocP1753

DOI: 10.3205/10dgnc224, URN: urn:nbn:de:0183-10dgnc2242

Published: September 16, 2010

© 2010 Stark et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

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Objective: Breast cancer is the second most common cause of brain metastases. We report on the genetic profiling of brain- and bone-selective invasive and metastatic MDA-MB-231 breast cancer cells using cDNA Array technology, real-time RT-PCR and protein detecting methods.

Methods: Gene profiling was performed using the 16K gene chip of the National Human Genome Research Institute, NIH, USA. Results were verified by real-time RT-PCR. Protein expression was examined using enzyme-linked immunosorbent assays (ELISA), western blotting and immunohistochemistry. Migration and invasion assays were performed with the QCM 96-well Migration/Invasion Assay +/- specific inhibitors.

Results: cDNA array analysis revealed significant over- or underexpression in brain- and / or bone-seeking cells of 113 genes. 9 gene sequences were chosen for data validation using real-time RT-PCR. Significant changes in both selective clones were found for: (1) matrix-metallo-proteinase 1 (MMP-1). Further examination revealed increased expression of MMP-1 and -9 in both selective clones on the mRNA and protein level. (2) metastasis suppressor gene KISS-1, Further examination of human tissue samples revealed reduced expression of several metastasis suppressor genes in breast cancer brain metastases versus primary tumors and normal breast tissue: Kai1, BRMS-1, Mkk-4, Maspin (SERPIN B5). (3) vascular factors endoglin and TIE-1. Endoglin was highly overexpressed in both selective clones and, moreover, was associated with matrix-metallo-proteinases -1 and -19 and was also associated with the cells migration and invasion capacity.

Conclusions: Several genes show significant over- or underexpression in brain-selective metastatic MDA-MB-231 clones. Herein, metastasis suppressor genes KiSS1, Kai1, BRMS-1, Mkk-4 and Maspin as well as matrix-metallo-proteinases -1 and -9 as well as vascular adhesion molecule endoglin are interesting candidates for future research.