Artikel
The cell cycle regulatory protein SCC-112 is upregulated in human malignant gliomas
Das Zellzyklus regulierende Protein SCC-112 ist in humanen malignen Gliomen hochreguliert
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Veröffentlicht: | 30. Mai 2008 |
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Gliederung
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Objective: Glioblastomas (GBM) are characterized by a high degreee of invasiveness and are highly aneuploid from an early stage. Normally, the mitotic cell cycle checkpoint ensures intact spindle mircrotubuli-binding to sister chromatids in the G2/M phase of the cell cycle. Defects in this checkpoint cause chromosomal instability and may be tumorigenic. SCC-112 is a cell cycle regulated protein with highest protein levels during G2/M phase. The relative research on SCC-112 has been few so far. SCC-112 has been shown to be downregulated in kidney and breast cancer, but upregulated in tumors of esophagus, liver, transverse colon, stomach, lung and uterus compared to the corresponding normal tissues. Its expression promotes cell proliferation. Here, we analysed human malignant gliomas for SCC-112 mRNA and protein expression.
Methods: SCC-112 cDNA was cloned from the rat PC12 phaeochromocytoma cell line. Its expression profile was tested in rat organs, C6 rat GBM cells, human GBM cell lines U87, U434, U373, U251 and GaMG and in a panel of 15 human astrocytomas WHO grade 2, 15 GBM and 3 normal brain samples from patients biopsies by semiquantitative RT-PCR, Western blotting and immunohistochemistry.
Results: Rat SCC-112 expression was detected in heart, kidney, muscle, spleen, and very strongly in testes but only weakly in brain samples. However, strong mRNA expression was seen in the rat GBM cell line C6. This finding suggested upregulation of SCC-112 in astrocytic tumors. Therefore, SCC-112 protein expression was assessed in several human GBM cell lines and human glioma tissue samples. All tested cell lines were positive and in tumors there was a clear increase in SCC-112 mRNA and protein expression detectable, corresponding with the WHO grade.
Conclusions: These results establish a potential oncogenic role for SCC-112 in tumorigenesis of human malignant gliomas. This is the first report of an altered protein expression in GBM and indicates that cell cycle regulated proteins might be potential therapeutic targets.