[en] Despite Glioblastoma (GBM) frequently expressing programmed cell death ligand-1 (PD-L1), treatment with anti-programmed cell death-1 (PD1) has not yielded brilliant results. Intratumor variability of PD-L1 can impact determination accuracy. A previous study on mouse embryonic fibroblasts (MEFs) reported a role for cyclin-D in control of PD-L1 expression. Because tumor-cell growth within a cancer is highly heterogeneous, we looked at whether PD-L1 and its cochaperone FKBP51s were influenced by cell proliferation, using U251 and SF767 GBM-cell-lines. PD-L1 was measured by Western blot, flow cytometry, confocal-microscopy, quantitative PCR (qPCR), CCND1 by qPCR, FKBP51s by Western blot and confocal-microscopy. Chromatin-Immunoprecipitation assay (xChIp) served to assess the DNA-binding of FKBP51 isoforms. In the course of cell culture, PD-L1 appeared to increase concomitantly to cyclin-D on G1/S transition, to decrease during exponential cell growth progressively. We calculated a correlation between CCND1 and PD-L1 gene expression levels. In the temporal window of PD-L1 and CCND1 peak, FKBP51s localized in ER. When cyclin-D declined, FKBP51s went nuclear. XChIp showed that FKBP51s binds CCND1 gene in a closed-chromatin configuration. Our finding suggests that the dynamism of PD-L1 expression in GBM follows cyclin-D fluctuation and raises the hypothesis that FKBP51s might participate in the events that govern cyclin-D oscillation.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Tufano, Martina ; Department of Molecular Medicine and Medical Biothecnology, University Federico II, 80131 Napoli, Italy
D'arrigo, Paolo ; Université de Liège - ULiège > Département des sciences de la vie > Virologie - Immunologie
D'Agostino, Massimo; Department of Molecular Medicine and Medical Biothecnology, University Federico II, 80131 Napoli, Italy
Giordano, Carolina; Istituto di Neuroscience, Università Cattolica S. Cuore, 00168 Roma, Italy
Marrone, Laura; Department of Molecular Medicine and Medical Biothecnology, University Federico II, 80131 Napoli, Italy
Cesaro, Elena; Department of Molecular Medicine and Medical Biothecnology, University Federico II, 80131 Napoli, Italy
Romano, Maria Fiammetta ; Department of Molecular Medicine and Medical Biothecnology, University Federico II, 80131 Napoli, Italy
Romano, Simona ; Department of Molecular Medicine and Medical Biothecnology, University Federico II, 80131 Napoli, Italy
Language :
English
Title :
PD-L1 Expression Fluctuates Concurrently with Cyclin D in Glioblastoma Cells.
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