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Resolving the EGF-E...
Resolving the EGF-EGFR interaction characteristics through a multiple-temperature, multiple-inhibitor, real-time interaction analysis approach
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- Björkelund, Hanna, 1983- (author)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
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- Gedda, Lars (author)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
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- Malmqvist, Magnus (author)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
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- Andersson, Karl (author)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
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(creator_code:org_t)
- 2012-10-30
- 2013
- English.
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In: Molecular and Clinical Oncology. - : Spandidos Publications. - 2049-9469 .- 2049-9450. ; 1:2, s. 343-352
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http://www.spandidos...
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https://www.spandido...
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https://urn.kb.se/re...
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https://doi.org/10.3...
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Abstract
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- Overexpression and aberrant activity of the epidermal growth factor (EGF) have been observed in various cancer types, rendering it an important target in oncology research. The interaction between EGF and its receptor (EGFR), as well as subsequent internalization, is complex and may be affected by various factors including tyrosine kinase inhibitors (TKIs). By combining real‑time binding curves produced in LigandTracer® with internalization assays conducted at different temperatures and with different TKIs, the processes of ligand binding, internalization and excretion was visualized. SKOV3 cells had a slower excretion rate compared to A431 and U343 cells, and the tested TKIs (gefitinib, lapatinib, AG1478 and erlotinib) reduced the degree of internalization. The kinetic analysis of the binding curves further demonstrated TKI‑dependent balances of EGFR monomer and dimer populations, where lapatinib promoted the monomeric form, while the other TKIs induced dimers. The dimer levels were found to be associated with the apparent affinity of the EGF‑EGFR interaction, with EGF binding stronger to EGFR dimers compared to monomers. This study analyzed how real‑time molecular interaction analysis may be utilized in combination with perturbations in order to understand the kinetics of a ligand‑receptor interaction, as well as some of its associated intracellular processes. Our multiple‑temperature and ‑inhibitor assay setup renders it possible to follow the EGFR monomer, dimer and internalized populations in a detailed manner, allowing for a new perspective of the EGFR biology.
Keyword
- epidermal growth factor
- tyrosine kinase inhibitors
- internalization
- kinetics
- dimerization
- heterogeneity
- Medicin
- Medicine
- Molecular Biotechnology
- Molekylär bioteknik
- Medical Cell Biology
- Medicinsk cellbiologi
Publication and Content Type
- ref (subject category)
- art (subject category)
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