CG&D
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kunz, M.
Right arrow Articles by Gross, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kunz, M.
Right arrow Articles by Gross, G.
Cell Growth & Differentiation Vol. 12, 137-145, March 2001
© 2001 American Association for Cancer Research

Activation of c-Jun NH2-Terminal Kinase/Stress-activated Protein Kinase (JNK/SAPK) Is Critical for Hypoxia-induced Apoptosis of Human Malignant Melanoma1

Manfred Kunz2, Saleh Ibrahim, Dirk Koczan, Hans-J. Thiesen, Hans J. Köhler, Till Acker, Karl H. Plate, Stephan Ludwig, Ulf R. Rapp, Eva-B. Bröcker, Goos N. P. van Muijen, Egbert Flory and Gerd Gross

Department of Dermatology and Venereology [M. K., G. G.] and Institute of Immunology [S. I., D. K., H-J. T., H. J. K.], University of Rostock, 18055 Rostock, Germany; Department of Neuropathology, University of Erlangen-Nürnberg, 91054 Erlangen, Germany [T. A., K. H. P.]; Institut für Medizinische Strahlenkunde und Zellforschung [S. L., U. R. R.] and Department of Dermatology [E-B. B.], University of Würzburg, 97080 Würzburg, Germany; Department of Pathology, University of Nijmegen, 6500 Nijmegen, the Netherlands [G. N. P. v. M.]; and Paul-Ehrlich-Institute, 63225 Langen, Germany [E. F.]

Mitogen-activated protein kinase (MAPK) signaling was examined in malignant melanoma cells exposed to hypoxia. Here we demonstrate that hypoxia induced a strong activation of the c-Jun NH2-terminal kinase (JNK), also termed stress-activated protein kinase (SAPK), in the melanoma cell line 530 in vitro. Other members of the MAPK family, e.g., extracellular signal-regulated kinase and p38, remained unaffected by the hypoxic stimulus. Activated JNK/SAPK could also be observed in the vicinity of hypoxic tumor areas in melanoma metastases as detected by immunohistochemistry. Functional analysis of JNK/SAPK activation in the melanoma cell line 530 revealed that activation of JNK/SAPK is involved in hypoxia-mediated tumor cell apoptosis. Both a dominant negative mutant of JNK/SAPK (SAPKß K->R) and a dominant negative mutant of the immediate upstream activator of JNK/SAPK, SEK1 (SEK1 K->R), inhibited hypoxia-induced apoptosis in transient transfection studies. In contrast, overexpression of the wild-type kinases had a slight proapoptotic effect. Inhibition of extracellular signal-regulated kinase and p38 pathways by the chemical inhibitors PD98058 and SB203580, respectively, had no effect on hypoxia-induced apoptosis. Under normoxic conditions, no influence on apoptosis regulation was observed after inhibition of all three MAPK pathways. In contrast to recent findings, JNK/SAPK activation did not correlate with Fas or Fas ligand (FasL) expression, suggesting that the Fas/FasL system is not involved in hypoxia-induced apoptosis in melanoma cells. Taken together, our data demonstrate that hypoxia-induced JNK/SAPK activation appears to play a critical role in apoptosis regulation of melanoma cells in vitro and in vivo, independent of the Fas/FasL system.




This article has been cited by other articles:


Home page
The OncologistHome page
A. Wouters, B. Pauwels, F. Lardon, and J. B. Vermorken
Review: Implications of In Vitro Research on the Effect of Radiotherapy and Chemotherapy Under Hypoxic Conditions
Oncologist, June 1, 2007; 12(6): 690 - 712.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
K. M. Comerford, E. P. Cummins, and C. T. Taylor
c-Jun NH2-Terminal Kinase Activation Contributes to Hypoxia-Inducible Factor 1{alpha}-Dependent P-Glycoprotein Expression in Hypoxia
Cancer Res., December 15, 2004; 64(24): 9057 - 9061.
[Abstract] [Full Text] [PDF]


Home page
J. Clin. Pathol.Home page
A E Greijer and E van der Wall
The role of hypoxia inducible factor 1 (HIF-1) in hypoxia induced apoptosis
J. Clin. Pathol., October 1, 2004; 57(10): 1009 - 1014.
[Abstract] [Full Text] [PDF]


Home page
J. Exp. Biol.Home page
K. L. Drew, M. B. Harris, J. C. LaManna, M. A. Smith, X. W. Zhu, and Y. L. Ma
Hypoxia tolerance in mammalian heterotherms
J. Exp. Biol., August 15, 2004; 207(18): 3155 - 3162.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
K. R. Laderoute, J. M. Calaoagan, M. Knapp, and R. S. Johnson
Glucose Utilization Is Essential for Hypoxia-Inducible Factor 1{alpha}-Dependent Phosphorylation of c-Jun
Mol. Cell. Biol., May 15, 2004; 24(10): 4128 - 4137.
[Abstract] [Full Text] [PDF]


Home page
J. Virol.Home page
B. Zhang, D. F. Spandau, and A. Roman
E5 Protein of Human Papillomavirus Type 16 Protects Human Foreskin Keratinocytes from UV B-Irradiation-Induced Apoptosis
J. Virol., January 1, 2002; 76(1): 220 - 231.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 2001 by the American Association of Cancer Research.