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Journal of Biomedicine and Biotechnology
Volume 2009 (2009), Article ID 451084, 10 pages
http://dx.doi.org/10.1155/2009/451084
Research Article

Mesothelioma Cells Escape Heat Stress by Upregulating Hsp40/Hsp70 Expression via Mitogen-Activated Protein Kinases

1Molecular Medicine Research Group, The Woolcock Institute for Medical Research, University of Sydney, 20 Missendon Road, Camperdown, NSW 2050, Australia
2Pulmonary Cell Research, Department of Internal Medicine and Research, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland
3Respiratory Cell Research & Pneumology, Lab 305, University Hospital Basel, Hebelstrasse 20, CH-4031 Basel, Switzerland

Received 23 February 2009; Accepted 6 April 2009

Academic Editor: Paul Higgins

Copyright © 2009 Michael Roth et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Therapy with hyperthermal chemotherapy in pleural diffuse malignant mesothelioma had limited benefits for patients. Here we investigated the effect of heat stress on heat shock proteins (HSP), which rescue tumour cells from apoptosis. In human mesothelioma and mesothelial cells heat stress (39–42°C) induced the phosphorylation of two mitogen activated kinases (MAPK) Erk1/2 and p38, and increased Hsp40, and Hsp70 expression. Mesothelioma cells expressed more Hsp40 and were less sensitive to heat stress compared to mesothelial cells. Inhibition of Erk1/2 MAPK by PD98059 or by Erk1 siRNA down-regulated heat stress-induced Hsp40 and Hsp70 expression and reduced mesothelioma cell survival. Inhibition of p38MAPK by SB203580 or siRNA reduced Hsp40, but not Hsp70, expression and also increased mesothelioma cell death. Thus hyperthermia combined with suppression of p38 MAPK or Hsp40 may represent a novel approach to improve mesothelioma therapy.