Einfluss der MAP-Kinase ERK3 (p97) auf EBV-positive Burkitt-Lymphom-Zellen

In previous papers it was shown that Epstein-Barr Virus (EBV), a double stranded-DNA-Virus of the herpes virus family, is able to immortalize B-Cells. This assists the development of cancer as the Burkitt-Lymphoma.It was also shown, that stimulation of Epstein-Barr-Virus-genome-positive Burkitt-Lymphoma-Cells with the ganglioside LM1 leads to the induction of cell differentiation processes and activates the EBV lytic viral cycle. This induces the expression of 24 genes including the MAP-Kinase ERK3 (p97).In order to decode the ERK3 (p97) function we designed an EKR3-expression vector in antisense direction, which finally leaded to an EKR3 (p97) overexpression on both RNA and protein level. The effects of an ERK3 (p97) overexpression on the viral lytic cycle and on cell differentiation were detected by different parameters as BZLF1, EA (early antigen), cell proliferation and DNA-synthesis rate. A clear activation of the viral lytic cycle was observed. In further experiments the connection between ERK3 (p97) and the related MAP-kinase ERK3 (p63) and the Proteinkinase C was investigated. In both cases a decrease of protein expression level of ERK3 (p63) and the Proteinkinase C could be observed in Raji cells showing an overexpression of ERK3 (p97). In conclusion ERK3 (p97) seems to be involved in regulation of ERK3 (p63) and Proteinkinase C pathways. In order to decode further signalling pathways, Raji-cells that showed an overexpression of ERK3 (p97) were treated with substances that are known to activate specific signalling pathways (TPA, anti-IgM, SB203580, Lactacystin). Again an activation of the viral lytic cycle could be shown, additionally multiplied by the treatment with signalling pathway-activating substances as TPA and anti-IgM. Furthermore ERK3 (p97) seemed to influence cell differentiation because a significant reduction of cell proliferation was shown in Raji-cells treated with both signalling pathway activating substances and the expression vector compared to Raji cells, which were only treated with different substances. Further investigation will have to show how the detection of signalling pathways of ERK3 (p97), especially the activation of the viral lytic cycle, might be of use for future therapies regarding EBV induced cancer.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2006

Author dc:creator

• Eckert, Stephanie

Contributors dc:contributor

• Ritter, Klaus

• info:eu-repo/classification/ddc/610
• Medizin
• Epstein-Barr-Virus
• Ganglioside
• MAP-Kinase
• Expressionsvektor
• Antisense-Nucleinsäuren
• Burkitt-Lymphom
• Signaltransduktion
• Polymerase-Ketten

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-114425%22

OAI record oai:identifier

https://publications.rwth-aachen.de/oai2d?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Apublications.rwth-aachen.de%3A52187