EGFR Expression in HER2-Driven Breast Cancer Cells

Area of Science:

• Oncology
• Molecular Biology
• Nanotechnology

Background:

• Epidermal growth factor receptor (HER2) is overexpressed in 20% of breast cancers.
• HER2, an orphan receptor, activates ligand-independently via homodimerization and heterodimerization with EGFR, HER3, and HER4.
• Heterodimerization is implicated in therapeutic resistance in HER2-overexpressing breast cancer.

Purpose of the Study:

• To develop a method for simultaneous detection of individual EGFR and HER2 receptors on breast cancer cell plasma membranes.
• To analyze plasma membrane expression levels and distribution of EGFR and HER2 in individual cells.

Main Methods:

• Specific labeling of EGFR and HER2 with quantum dot nanoparticles (QDs).
• Correlative fluorescence microscopy and liquid phase electron microscopy for single-cell analysis.
• Quantification of QD-labeled receptor surface densities.

Main Results:

• Heterogeneous expression of EGFR and HER2 observed within the cell population and on individual SKBR3 breast cancer cells.
• QD-labeled EGFR surface density: (0.5-5) × 10¹ QDs/µm².
• QD-labeled HER2 surface density: (2-10) × 10² QDs/µm².
• EGFR enrichment observed at plasma membrane protrusions and in a subpopulation of EGFR-enriched cells.

Conclusions:

• A novel QD-based method enables simultaneous detection and quantification of EGFR and HER2.
• Demonstrated heterogeneous expression of EGFR and HER2, with distinct distribution patterns.
• Identified a novel EGFR-enriched cell subpopulation, potentially relevant for therapeutic resistance mechanisms.