Comparing the epidermal growth factor interaction with four different cell lines: intriguing effects imply strong dependency of cellular context.

The interaction of the epidermal growth factor (EGF) with its receptor (EGFR) is known to be complex, and the common over-expression of EGF receptor family members in a multitude of tumors makes it important to decipher this interaction and the following signaling pathways. We have investigated the...

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Main Authors: Hanna Björkelund, Lars Gedda, Karl Andersson
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3031572?pdf=render
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author Hanna Björkelund
Lars Gedda
Karl Andersson
author_facet Hanna Björkelund
Lars Gedda
Karl Andersson
author_sort Hanna Björkelund
collection DOAJ
description The interaction of the epidermal growth factor (EGF) with its receptor (EGFR) is known to be complex, and the common over-expression of EGF receptor family members in a multitude of tumors makes it important to decipher this interaction and the following signaling pathways. We have investigated the affinity and kinetics of (125)I-EGF binding to EGFR in four human tumor cell lines, each using four culturing conditions, in real time by use of LigandTracer®.Highly repeatable and precise measurements show that the overall apparent affinity of the (125)I-EGF - EGFR interaction is greatly dependent on cell line at normal culturing conditions, ranging from K(D) ≈ 200 pM on SKBR3 cells to K(D)≈8 nM on A431 cells. The (125)I-EGF - EGFR binding curves (irrespective of cell line) have strong signs of multiple simultaneous interactions. Furthermore, for the cell lines A431 and SKOV3, gefitinib treatment increases the (125)I-EGF - EGFR affinity, in particular when the cells are starved. The (125)I-EGF - EGFR interaction on cell line U343 is sensitive to starvation while as on SKBR3 it is insensitive to gefitinib and starvation.The intriguing pattern of the binding characteristics proves that the cellular context is important when deciphering how EGF interacts with EGFR. From a general perspective, care is advisable when generalizing ligand-receptor interaction results across multiple cell-lines.
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spelling doaj.art-08542bdac1ff4ace971ed0986653efec2022-12-21T19:44:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0161e1653610.1371/journal.pone.0016536Comparing the epidermal growth factor interaction with four different cell lines: intriguing effects imply strong dependency of cellular context.Hanna BjörkelundLars GeddaKarl AnderssonThe interaction of the epidermal growth factor (EGF) with its receptor (EGFR) is known to be complex, and the common over-expression of EGF receptor family members in a multitude of tumors makes it important to decipher this interaction and the following signaling pathways. We have investigated the affinity and kinetics of (125)I-EGF binding to EGFR in four human tumor cell lines, each using four culturing conditions, in real time by use of LigandTracer®.Highly repeatable and precise measurements show that the overall apparent affinity of the (125)I-EGF - EGFR interaction is greatly dependent on cell line at normal culturing conditions, ranging from K(D) ≈ 200 pM on SKBR3 cells to K(D)≈8 nM on A431 cells. The (125)I-EGF - EGFR binding curves (irrespective of cell line) have strong signs of multiple simultaneous interactions. Furthermore, for the cell lines A431 and SKOV3, gefitinib treatment increases the (125)I-EGF - EGFR affinity, in particular when the cells are starved. The (125)I-EGF - EGFR interaction on cell line U343 is sensitive to starvation while as on SKBR3 it is insensitive to gefitinib and starvation.The intriguing pattern of the binding characteristics proves that the cellular context is important when deciphering how EGF interacts with EGFR. From a general perspective, care is advisable when generalizing ligand-receptor interaction results across multiple cell-lines.http://europepmc.org/articles/PMC3031572?pdf=render
spellingShingle Hanna Björkelund
Lars Gedda
Karl Andersson
Comparing the epidermal growth factor interaction with four different cell lines: intriguing effects imply strong dependency of cellular context.
PLoS ONE
title Comparing the epidermal growth factor interaction with four different cell lines: intriguing effects imply strong dependency of cellular context.
title_full Comparing the epidermal growth factor interaction with four different cell lines: intriguing effects imply strong dependency of cellular context.
title_fullStr Comparing the epidermal growth factor interaction with four different cell lines: intriguing effects imply strong dependency of cellular context.
title_full_unstemmed Comparing the epidermal growth factor interaction with four different cell lines: intriguing effects imply strong dependency of cellular context.
title_short Comparing the epidermal growth factor interaction with four different cell lines: intriguing effects imply strong dependency of cellular context.
title_sort comparing the epidermal growth factor interaction with four different cell lines intriguing effects imply strong dependency of cellular context
url http://europepmc.org/articles/PMC3031572?pdf=render
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