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Rat mesothelioma cell proliferation requires p38δ mitogen activated protein kinase and C/EBP-α

Zhong, J. and Lardinois, D. and Szilard, J. and Tamm, M. and Roth, M.. (2011) Rat mesothelioma cell proliferation requires p38δ mitogen activated protein kinase and C/EBP-α. Lung cancer, Vol. 73, H. 2. pp. 166-170.

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Official URL: http://edoc.unibas.ch/dok/A6007051

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Abstract

Pleural malignant mesothelioma is a rare but deadly tumour mainly induced by asbestos inhalation. Despite the ban of asbestos in 1990 in 52 countries, mesothelioma cases still increase worldwide. In pleural mesothelioma, p38 mitogen activated protein kinases (MAPK) have been suggested to play a major role in carcinogenesis and aggressiveness of tumours. The aim of this study was to determine the role of the different four p38 MAPK isoforms and their effect on proliferation together with the underlying signalling pathways in a rat pleural mesothelioma cell line. Rat pleural mesothelioma cells were stimulated with platelet-derived growth factor (PDGF)-BB and/or transforming growth factor beta (TGF)-?. MAPK and transcription factor expression and activation was monitored in the cytosol and nucleus by immuno-blotting. Proliferation was determined by manual cell count and siRNAs were used to control MAPK and transcription factor expression and action. Only PDGF-BB, but not TGF-?1 induced proliferation via activated Erk1/2 and p38 MAPK. The p38? and ? isoforms were expressed in the cytosol, and upon activation p38? translocated into the nucleus, while p38? remained in the cytosol. No other p38 isoform was expressed by rat mesothelioma cells. C/EBP-? was found in both the cytosol and the nucleus, while C/EBP-? was not expressed at all. PDGF-BB induced proliferation was suppressed by down-regulation of either Erk1/2, or p38? MAPK, or C/EBP-?. Furthermore, TGF-? inhibited PDGF-BB induced proliferation by interruption of p38 MAPK signalling. From this rat model, we conclude that in pleural mesothelioma, p38? in C/EBP-? mediate proliferation and thus may represent new targets in mesothelioma therapy.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Pulmonary Cell Research (Roth/Tamm)
03 Faculty of Medicine > Bereich Operative Fächer (Klinik) > Innere Organe > Thoraxchirurgie (Lardinois)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Operative Fächer (Klinik) > Innere Organe > Thoraxchirurgie (Lardinois)
UniBasel Contributors:Lardinois, Didier and Tamm, Michael and Roth-Chiarello, Michael
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Elsevier
ISSN:0169-5002
Note:Variant title: Rat mesothelioma cell proliferation requires p38delta mitogen activated protein kinase and C/EBP-alpha -- Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 May 2015 08:45
Deposited On:31 Jan 2014 09:49

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