Artikel
Increased expression of the transcription factor and proto-oncogene Ets-1 within the invasion area of human low-grade gliomas
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Autoren
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T. Kratzsch
- Max Delbrück Center for Molecular Medicine, Experimental Pharmacology, Berlin, Deutschland
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S. Pfeifenbring
- Institute of Neuropathology, University Medicine, Göttingen, Deutschland
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U. Träger
- Department of Neurosurgery, Ernst von Bergmann Hospital Potsdam, Deutschland
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I. Fichtner
- Max Delbrück Center for Molecular Medicine, Experimental Pharmacology, Berlin, Deutschland
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S.A. Kuhn
- Max Delbrück Center for Molecular Medicine, Experimental Pharmacology, Berlin, Deutschland; Department of Neurosurgery, Ernst von Bergmann Hospital Potsdam, Deutschland
| Veröffentlicht: | 4. Juni 2012 |
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Gliederung
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Objective: Ets-1 is a regulatory transcription factor and proto-oncogene and is shown to be expressed physiologically in angiogenesis and vasculogenesis, as well as pathologically in conditions of inflammatory or neoplastic neoangiogenesis. There are no reports about its expression in human low-grade oligodendrogliomas and oligoastrocytomas.
Methods: Study was approved by the local ethics committee. Human glioma cells were implanted subcutaneously into immunocompromised mice (n=20). Low-grade gliomas (astro, oligo, and mixed) were investigated immunohistochemically for Ets-1 expression. Tumor samples were evaluated for their peritumoral brain tissue, area of invasion, and area of compact tumor mass. Brain tissue from autopsy series was taken as controls. Statistical analyses were performed by SPSS. Correlation was studied by the Spearman Rho test. Statistical significance was considered for α<0.05.
Results: We detected a specific immunohistochemical Ets-1 expression pattern in low-grade gliomas. Tumor cells of gliomas WHO II° demonstrated a clear Ets-1 expression; the intensity and frequency of the cellular Ets-1 staining varied according to the tumor region. A positive cytoplasmic Ets-1 staining was visible within the tumor center and correlated with the mitotic rate of tumor tissue. Nuclear Ets-1 expression was observed within the area of invasion and correlated with the transcriptionally active Ets-1 variant. Non-neoplastic glial cells of human control brain tissue did not express Ets-1 at all. Subcutaneously xenotransplanted human gliomas displayed the same expression pattern as did the primary patient samples.
Conclusions: Here, we demonstrated for the first time a locally regulated expression of Ets-1 in low-grade gliomas. The non-invasive tumor center showed inactive cytoplasmic Ets-1, which strongly correlated with a high mitotic rate and confirmed the hypothesis of either invading or growing tumor cells. The nuclear Ets-1 expression was displayed at the invasive edge, which confirms the important role of Ets-1 in glioma invasion and neoangiogenesis. Xenotransplanted gliomas confirmed all human results in a model system that enables further analyses of the Ets-1 role in glioma invasion.
