help button home button Am J Pathol ASIP MEMBERSHIP
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
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 reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Xu, Y.
Right arrow Articles by Fisher, G. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Xu, Y.
Right arrow Articles by Fisher, G. J.
(American Journal of Pathology. 2006;169:823-830.)
© 2006 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2006.050449

Epidermal Growth Factor Receptor Is a Critical Mediator of Ultraviolet B Irradiation-Induced Signal Transduction in Immortalized Human Keratinocyte HaCaT Cells

Yiru Xu, John J. Voorhees and Gary J. Fisher

From the Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan

Epidermal growth factor receptor (EGFR) is a critical mediator of several types of epithelial cancers. Skin cancer arising from exposure to ultraviolet B irradiation (UVB) from the sun is a prominent form of human cancer. Recent data indicate that in addition to cognate ligands, EGFR is activated by UVB irradiation. We used pharmacological and genetic approaches to investigate the function of EGFR in mediating UVB-induced signal transduction in human skin keratinocyte HaCaT cells. Pharmacological inhibition of EGFR tyrosine kinase significantly inhibited UVB-mediated induction of ERK, p38, and JNK MAP kinases, and their effectors, transcription factors c-Fos and c-Jun. Inhibition of UVB activation of EGFR also suppressed activation of AKT-, PKC-, and PKA-dependent signal transduction pathways. B82 mouse L cells devoid of EGFR were used to further investigate EGFR dependence of UVB-induced signal transduction. UVB failed to induce ERK, and JNK activation was reduced 60% in B82 cells compared to B82K+ cells, which express EGFR. In addition, UVB induced both c-Fos and c-Jun proteins in B82K+ cells, whereas neither were induced in B82 cells. Taken together, these data demonstrate that EGFR is required for UVB-mediated induction of multiple signaling pathways that are known to mediate tumor formation in skin.




This article has been cited by other articles:


Home page
 Sci SignalHome page
P. Agostinis, M. Garmyn, and A. Van Laethem
The Aryl Hydrocarbon Receptor: An Illuminating Effector of the UVB Response
Sci. Signal., September 11, 2007; 2007(403): pe49 - pe49.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
E. Fritsche, C. Schafer, C. Calles, T. Bernsmann, T. Bernshausen, M. Wurm, U. Hubenthal, J. E. Cline, H. Hajimiragha, P. Schroeder, et al.
Lightening up the UV response by identification of the arylhydrocarbon receptor as a cytoplasmatic target for ultraviolet B radiation
PNAS, May 22, 2007; 104(21): 8851 - 8856.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. Singhirunnusorn, Y. Ueno, M. Matsuo, S. Suzuki, I. Saiki, and H. Sakurai
Transient Suppression of Ligand-mediated Activation of Epidermal Growth Factor Receptor by Tumor Necrosis Factor-{alpha} through the TAK1-p38 Signaling Pathway
J. Biol. Chem., April 27, 2007; 282(17): 12698 - 12706.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2006 by the American Society for Investigative Pathology.