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Regulation of Bcl-xL expression in human keratinocytes by cell–substratum adhesion and the epidermal growth factor receptor
Journal article   Open access

Regulation of Bcl-xL expression in human keratinocytes by cell–substratum adhesion and the epidermal growth factor receptor

Ulrich Rodeck, Monika Jost, James DuHadaway, Csaba Kari, Pamela J Jensen, Barbara Risse and Donald L Ewert
Proceedings of the National Academy of Sciences - PNAS, v 94(10), pp 5067-5072
13 May 1997
PMID: 9144191
url
https://doi.org/10.1073/pnas.94.10.5067View
Published, Version of Record (VoR)Open Access (License Unspecified) Open

Abstract

Biological Sciences
Cell–substratum adhesion is an essential requirement for survival of human neonatal keratinocytes in vitro . Similarly, activation of the epidermal growth factor receptor (EGF-R) has recently been implicated not only in cell cycle progression but also in survival of normal keratinocytes. The mechanisms by which either cell–substratum adhesion or EGF-R activation protect keratinocytes from programmed cell death are poorly understood. Here we describe that blockade of the EGF-R and inhibition of substratum adhesion share a common downstream event, the down-regulation of the cell death protector Bcl-x L . Expression of Bcl-x L protein was down-regulated during forced suspension culture of keratinocytes, concurrent with large-scale apoptosis. Similarly, EGF-R blockade was accompanied by down-regulation of Bcl-x L steady-state mRNA and protein levels to an extent comparable to that observed in forced suspension culture. However, down-regulation of Bcl-x L expression by EGF-R blockade was not accompanied by apoptosis; in this case, a second signal, generated by passaging, was required to induce rapid and large-scale apoptosis. These findings are consistent with the conclusions that ( i ) Bcl-x L represents a shared molecular target for signaling through cell-substrate adhesion receptors and the EGF-R, and ( ii ) reduced levels of Bcl-x L expression through EGF-R blockade lower the tolerance of keratinocytes for cell death signals generated by cellular stress.

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Domestic collaboration
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Multidisciplinary Sciences
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