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Updated: Apr 8, 2026

Validated Immunochemical Assay for Comprehensive Determination of the Human Epidermal Growth Factor Receptor 2 Released from and Bound to Cells
Published on: May 9, 2025
VERO stable cell lines expressing full-length human epidermal growth factor receptors 2 and 3: platforms for
Akbar Hedayatizadeh-Omran1, Reza Valadan1,2, Alireza Rafiei1,2
11 Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences , Sari, Iran .
Abstract:
Cross-talk between human epidermal growth factor receptor 2 and 3 (HER2 and HER3) may potentially contribute to therapeutic resistance in human breast cancer. Subtractive phage display allows highly specific selection for antibody fragments directed against cells surface HER2 and HER3. The strategies to select conformation- and activation-specific antibodies against HER2 and HER3 require tightly regulated HER2 and HER3 expressing cells that allow controlled activation/inactivation of these receptors during panning procedures. To achieve this, first, we found that the VERO cell line is an appropriate cell line for heterogeneous expression of HER2 and HER3, and then we established a panel of VERO stable cell lines expressing high levels of HER2 and HER3 alone and in combination. We also showed that HER2 and HER3 expressed in VERO cells were biologically active and could form heterodimer following neuregulin1 treatment. The cell line established here not only provided platforms for phage display-based methods but also could be used in any HER-related studies.
Insights
Researchers developed specific cell lines to study resistance in breast cancer. These VERO cell lines expressing human epidermal growth factor receptors 2 and 3 (HER2 and HER3) enable new antibody development for targeted therapies.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Cross-talk between human epidermal growth factor receptor 2 (HER2) and human epidermal growth factor receptor 3 (HER3) is implicated in therapeutic resistance in breast cancer.
- Developing targeted therapies requires specific antibodies against HER2 and HER3.
Purpose of the Study:
- To establish a cell line system for selecting conformation- and activation-specific antibodies against HER2 and HER3.
- To provide a platform for subtractive phage display methods targeting HER2 and HER3.
Main Methods:
- Utilized VERO cells for heterogeneous expression of HER2 and HER3.
- Established stable VERO cell lines expressing high levels of HER2 and HER3, individually and in combination.
- Assessed biological activity and heterodimerization of expressed HER2 and HER3 upon neuregulin1 treatment.
Main Results:
- VERO cells are suitable for heterogeneous expression of HER2 and HER3.
- Established VERO cell lines with controlled expression of HER2 and HER3.
- Demonstrated that HER2 and HER3 expressed in VERO cells are biologically active and form heterodimers.
Conclusions:
- The developed VERO cell lines provide a robust platform for phage display and antibody selection against HER2 and HER3.
- These cell lines can be utilized for various HER-related research, aiding in understanding and overcoming therapeutic resistance in breast cancer.
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