Artikel
The mitochondrial ribosome function protein MRP-L32 is associated with malignancy of human glial tumors
Das mitochondriale Ribosom-Funktionsprotein MRP-L32 ist assoziiert mit der Malignität glialer Tumoren
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Autoren
Veröffentlicht: | 4. Mai 2005 |
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Gliederung
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Objective
Mitochondria play an important role in therapeutically induced apoptosis of tumor cells. To analyze the prognostic role of mitochondrial morphology, we studied gliomas of varying dignity with respect to possible prognostic prediction, using MRP-L32, a phosphorylation associated mitochondrially encoded ribosomal function protein.
Methods
We used a novel antibody to MRP-L32 with the indirect peroxidase technique on paraffin-embedded tissue of normal human brain and 136 glial tumors of varying dignity WHO grade I-IV. For comparison, localization of the protein was studied in primary cell cultures of glioblastoma (n=6) using oregon green or Cy3-labeled secondary antibody. In addition we studied proliferation (MIB-1) and MTCO2 for mitochondrial numbers. Immunoreaction (IR) was evaluated using a semiquantative scoring system and statistical evaluation with the chi square test.
Results
We found a low constitutive expression of MRP-L32 in normal human brain, mostly in astrocytes with emphasis on subependymal and perivascular astrocytes. There was no increased IR in benign gliomas. In malignant gliomas, approximately 40% of the cases showed strongly increased IR. We found a signifiant association with malignancy, though without difference between grades III and IV tumors There was no correlation with proliferation within glioblastomas or with mitochondrial frequencies.
Conclusions
The observed results suggest a dichotomy of malignant tumors with regard to the expression of MRP-L32, which is not dependent on mitochondrial frequencies. It still has to be established whether this is due to a genetic or a pathway - related effect. Results further suggest that the protein may provide an identification of different subtypes of malignant gliomas, sensitive to different treatment protocols.