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A central role of Bcl-X(L) in the regulation of keratinocyte survival by autocrine EGFR ligands
Journal article   Open access   Peer reviewed

A central role of Bcl-X(L) in the regulation of keratinocyte survival by autocrine EGFR ligands

M Jost, R Class, C Kari, P J Jensen and U Rodeck
Journal of investigative dermatology, v 112(4), pp 443-449
Apr 1999
DOI: https://doi.org/10.1046/j.1523-1747.1999.00543.x
PMID: 10201527
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1046/j.1523-1747.1999.00543.xView
Published, Version of Record (VoR)Open Access (Publisher-Specific),  Open

Abstract

Transforming Growth Factor beta - pharmacology bcl-X Protein Proto-Oncogene Proteins c-bcl-2 - physiology Cell Cycle Cell Survival Humans Cells, Cultured Receptor, Epidermal Growth Factor - physiology Apoptosis Keratinocytes - physiology
The epidermal growth factor receptor has multiple roles in epidermal biology relating to growth, migration, and, as shown recently, survival of keratinocytes. In cultured keratinocytes activation of the epidermal growth factor receptor upregulates expression of Bcl-x(L), an anti-apoptotic Bcl-2 homolog. The functional contribution of epidermal growth factor receptor-dependent Bcl-x(L) expression to keratinocyte survival is poorly understood. Here we demonstrate that inhibition of the epidermal growth factor receptor tyrosine kinase activity with either an epidermal growth factor receptor antagonistic monoclonal antibody (MoAb 425) or an epidermal growth factor receptor-selective tyrosine kinase inhibitor (AG 1478) downregulated Bcl-x(L) expression in normal human keratinocytes but had no effect on expression of the pro-apoptotic Bcl-2 homologs Bad, Bak, and Bax. Bovine pituitary extract and insulin partially alleviated both, downregulation of Bcl-x(L) expression and cell death upon epidermal growth factor receptor inhibition. Forced expression of Bcl-x(L) attenuated cell death of immortalized keratinocytes (HaCaT) induced by either forced suspension (anoikis) or by epidermal growth factor receptor blockade. These results demonstrate that epidermal growth factor receptor-dependent signaling pathways control the balance of pro-apoptotic and anti-apoptotic Bcl-2 family members expressed in normal keratinocytes. Inappropriate survival supported by aberrant signaling through the epidermal growth factor receptor may contribute to the pathogenesis of psoriasis and of squamous cell carcinomas.

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Collaboration types
Domestic collaboration
Web of Science research areas
Dermatology
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