TERT and its binding protein: overexpression of GABPA/B in high grade gliomas
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Efthymios Papazacharias1, Saskia Kuhl1, Gabriele Röhn1, Lukas Görtz1, Roland Goldbrunner1 and Marco Timmer1
1 Laboratory of Neurooncology and Experimental Neurosurgery, Department of General Neurosurgery, Center for Neurosurgery, Faculty of Medicine and University Hospital, University of Cologne, Cologne, Germany
Keywords: TERT; GABPA; GABPB; glioma; astrocytoma
Received: November 13, 2020 Accepted: March 22, 2021 Published: June 22, 2021
Enhanced expression of TERT in gliomas is a result of two hotspot mutations, C228T and C250T, at the promoter region. GA-binding proteins selectively bind at these positions, respectively, causing an activation of the promoter and overexpression of TERT. GABP is a multimeric protein consisting of GABPA and GABPB with its isoforms GABPB1, GABPB1-L, GABPB1-S, GABPB2.
In this study, we investigated the mRNA expression and association between TERT and GABPA/B isoforms in tumor samples of different glioma grades. The expression was determined by quantitative real-time PCR and the results were statistically analyzed.
We present that TERT is mainly expressed in primary glioblastomas. All GA-binding proteins progress through the glioma grades and have the highest expression levels in secondary glioblastomas. In secondary glioblastomas after chemotherapy, GABPB1 and GABPB1-L are expressed on a lower level than without treatment. In high grades, TERT and GABPA, GAPB1, GABPB1-L, GABPB1-S are upregulated compared to low grades. Between primary and secondary glioblastomas with and without chemotherapy, TERT is elevated in the former while GABPB1 is increased in the secondary glioblastomas. GABPA and GABPB1, GABPB1-L and GABPB1-S positive correlate in primary glioblastomas.
The present study confirms the upregulation of TERT in primary glioblastomas while all GABP proteins rise with the malignancy of the gliomas. Further investigations must be made to elucidate the relation between TERT and all GABP proteins as it may play a key role in the gliomagenesis.
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