Publication Date:
2016-12-02
Description:
P53 plays a pleiotropic role in cell homeostasis by regulating stress-induced adaptive responses leading to survival or cell death. Although it is well demonstrated that the lack of a functional p53 pathway favors cancers, it remains still unclear whether it is related to its genome guardian or in apoptosis inducer role. Leonova and Gudkov demonstrated that, at least in mice, p53 and CpG methylation prevent expression of the so-called junk DNA, expression of which induces suicidal IFN responses (PNAS 2013;110:E89). Cancer cells mostly harbor hypo methylated DNA, reversible or irreversible silencing of p53 pathway and defects in suicidal IFN responses. Although the molecular bases are still not well understood, oncolytic viruses such as the Measles Virus (MV) preferentially infect and kill tumor cells. The aim of this study was to investigate whether del(17p)+/p53 mutant myeloma cells were preferentially sensitive to the Schwarz vaccine MV strain and whether p53 was involved in. Plasma cells from patients with multiple myeloma (MM) or MGUS over express CD46, the main receptor for the vaccine MV strain, as compared to normal plasma cells and to hematopoietic cells. To assess MV infection and replication, we used the GFP modified strain (MV-GFP) and measured GFP expression at day 4 after infection (MOI=1) using flow cytometry. We showed that p53 abnormal MM cell lines (n=25) over expressed CD46 (p=0.039) and were preferentially infected by MV (p=0.03) as compared with p53 wild type MM cell lines (n=12). Expressions of CD46 and GFP were directly correlated (p=0.014, r=0.505) and GFP expression correlated with cell death (n=37, p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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