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; Donald L Ewert

doi:10.1073/pnas.94.10.5067

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

Journal article

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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

DOI: https://doi.org/10.1073/pnas.94.10.5067

PMID: 9144191

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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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Details

Title: Regulation of Bcl-xL expression in human keratinocytes by cell–substratum adhesion and the epidermal growth factor receptor
Creators: Ulrich Rodeck - The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104; and
Monika Jost - The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104; and
James DuHadaway - The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104; and
Csaba Kari - The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104; and
Pamela J Jensen - The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104; and
Barbara Risse - The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104; and
Donald L Ewert - The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104; and
Publication Details: Proceedings of the National Academy of Sciences - PNAS, v 94(10), pp 5067-5072
Publisher: The National Academy of Sciences of the USA
Resource Type: Journal article
Language: English
Academic Unit: Intensive Medical Sciences (IMS)
Web of Science ID: WOS:A1997WZ25700046
Scopus ID: 2-s2.0-0030612602
Other Identifier: 991014878015404721

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Collaboration types: Domestic collaboration
Web of Science research areas: Multidisciplinary Sciences