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EGFR Expression in HER2-Driven Breast Cancer Cells

  • The epidermal growth factor receptor HER2 is overexpressed in 20% of breast cancer cases. HER2 is an orphan receptor that is activated ligand-independently by homodimerization. In addition, HER2 is able to heterodimerize with EGFR, HER3, and HER4. Heterodimerization has been proposed as a mechanism of resistance to therapy for HER2 overexpressing breast cancer. Here, a method is presented for the simultaneous detection of individual EGFR and HER2 receptors in the plasma membrane of breast cancer cells via specific labeling with quantum dot nanoparticles (QDs). Correlative fluorescence microscopy and liquid phase electron microscopy were used to analyze the plasma membrane expression levels of both receptors in individual intact cells. Fluorescent single-cell analysis of SKBR3 breast cancer cells dual-labeled for EGFR and HER2 revealed a heterogeneous expression for receptors within both the cell population as well as within individual cells. Subsequent electron microscopy of individual cells allowed the determination of individual receptors label distributions. QD-labeled EGFR was observed with a surface density of (0.5–5) × 101 QDs/µm2, whereas labeled HER2 expression was higher ranging from (2–10) × 102 QDs/µm2. Although most SKBR3 cells expressed low levels of EGFR, an enrichment was observed at large plasma membrane protrusions, and amongst a newly discovered cellular subpopulation termed EGFR-enriched cells.

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Document Type:Article
Author:Florian Weinberg, Diana B. PeckysORCiD, Niels de JongeORCiD
Parent Title (English):International Journal of Molecular Sciences
Year of first Publication:2020
Release Date:2022/11/18
Tag:EGFR; HER2; correlative microscopy; dual labeling; electron microscopy; single molecule
Impact:05.923 (2020)
Funding Information:Else Kröner-Frisenius-Stiftung through the project “Investigation of the Influence of Breast Cancer Drugs on HER2 Dimerization at the Molecular Level in Individual Cells Aiming to Find Clues for Causes of Drug Resistance: HERe”, and by the DFG SFB1027 (project C7).
Groups:Innovative Elektronenmikroskopie
Open Access:Open Access
Signature:INM 2020/136
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International