Related Experiment Video
Updated: May 3, 2026
Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017
Sensitivity of human granulosa cell tumor cells to epidermal growth factor receptor inhibition
Noora Andersson1, Mikko Anttonen, Anniina Färkkilä
1Children's Hospital, University of Helsinki and Helsinki University Central Hospital, PO Box 20, 00014 University of Helsinki, Finland Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, PO Box 140, 00290 Helsinki, Finland Department of Pathology, Helsinki University Central Hospital, University of Helsinki and HUSlab, Haartmaninkatu 3, 00290 Helsinki, Finland Department of Pediatrics, Washington University School of Medicine, St Louis Children's Hospital, St Louis, Missouri 63110, USA.
Abstract:
Epidermal growth factor receptor (EGFR) is implicated in the progression of many human cancers, but its significance in ovarian granulosa cell tumor (GCT) pathobiology remains poorly understood. We assessed the EGFR gene copy number, surveyed the mRNA and protein expression patterns of EGFR in 90 adult GCTs, and assessed the in vitro sensitivity of GCT cells to EGFR inhibition. Low-level amplification of EGFR gene was observed in five GCTs and high-level amplification in one sample. EGFR mRNA was robustly expressed in GCTs. Most tumors expressed both unphosphorylated and phosphorylated EGFR protein, but the protein expression did not correlate with clinical parameters, including the risk of recurrence. Small-molecule EGFR inhibitors reduced the EGF-induced activation of EGFR and its downstream signaling molecules at nanomolar doses, but cell viability was reduced, and caspase-3/7 was activated in GCT cells only at micromolar doses. Based on the present results, EGFR is active and abundantly expressed in the majority of GCTs, but probably has only minor contribution to GCT cell growth. Given the high doses of EGFR inhibitors required to reduce GCT cell viability in vitro, they are not likely to be effective for GCT treatment as single agents; they should rather be tested as part of combination therapies for these malignancies.
Insights
Epidermal growth factor receptor (EGFR) is highly expressed in ovarian granulosa cell tumors (GCTs). However, EGFR inhibitors show limited efficacy as single agents, suggesting combination therapy for GCT treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Epidermal growth factor receptor (EGFR) plays a role in various human cancers.
- The significance of EGFR in ovarian granulosa cell tumor (GCT) pathobiology is not well understood.
Purpose of the Study:
- To investigate EGFR gene copy number, mRNA, and protein expression in GCTs.
- To evaluate the in vitro sensitivity of GCT cells to EGFR inhibition.
Main Methods:
- Analysis of EGFR gene copy number in 90 adult GCTs.
- Assessment of EGFR mRNA and protein expression via quantitative PCR and immunohistochemistry.
- In vitro testing of GCT cell sensitivity to EGFR inhibitors.
Main Results:
- EGFR gene amplification was observed in a small subset of GCTs.
- EGFR mRNA and protein were robustly expressed in most GCTs, but without correlation to clinical parameters.
- EGFR inhibitors effectively blocked EGFR signaling at nanomolar doses but required micromolar doses to impact GCT cell viability.
Conclusions:
- EGFR is actively expressed in most GCTs but likely contributes minimally to tumor growth.
- EGFR inhibitors are unlikely to be effective as monotherapy for GCTs.
- Combination therapies involving EGFR inhibitors may hold potential for GCT treatment.
More Related Videos
08:28Validated Immunochemical Assay for Comprehensive Determination of the Human Epidermal Growth Factor Receptor 2 Released from and Bound to Cells
Published on: May 9, 2025
08:52Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
Published on: November 22, 2021
