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Updated: May 22, 2026
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Epidermal growth factor receptor signaling pathway involved in progestin-resistance of human endometrial carcinoma:
Yanli Xu1, Jianqian Tong, Zhihong Ai
1Department of Obstetrics and Gynecology, The Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
Aim:
The aim of these investigations was to study the role of gefitinib (a specific oral epidermal growth factor receptor-tyrosine kinase inhibitor) on reversing progestin-resistance in a human endometrial carcinoma xenograft model.
Material And Methods:
To study the effect of gefitinib and epidermal growth factor receptor (EGFR) overexpression on tumor progestin resistance, the Ishikawa endometrial carcinoma cell line was transfected to stably express a high level of EGFR, which resulted in the progestin-resistant Ishikawa-pLWERNL subcell line. BALB/c nude mice were injected subcutaneously with the parental Ishikawa cell line and the Ishikawa-pLWERNL cell line. Therapy experiments with gefitinib alone or in combination with medroxyprogesterone acetate (MPA) were done and samples were analyzed for EGFR and progesterone receptor isoform B (PR-B) expression by Western blot and immumohistochemistry analyses. Role in blocking EGFR autophosphorylation and its downstream signaling pathway and antagonizing progestin resistance by gefitinib was investigated by Western blot analysis.
Results:
EGFR expression was higher in progestin-resistant Ishikawa-pLWERNL endometrial cancer (EC) xenografts than in progestin-sensitive Ishikawa EC xenografts; in contrast, PR-B was higher in Ishikawa xenografts than in Ishikawa-pLWERNL xenografts. Higher EGFR expression reduced sensitivity to progestin and decreased PR-B expression in Ishikawa xenografts; it also abnormally activated EGFR autophosphorylation and its downstream signaling pathway. Gefitinib effectively inhibited the proliferation of EC xenografts that overexpressed EGFR, and reversed hormone resistance in progestin-resistant EC xenografts.
Discussion:
The present study describes an in vivo model that can provide a valuable tool in studying the interaction of overexpressed EGFR and progestin resistance in EC. Gefitinib may be useful in the treatment of progestin-resistant EC.
Insights
Gefitinib, an epidermal growth factor receptor inhibitor, reversed progestin resistance in endometrial cancer xenografts. This study highlights gefitinib
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Progestin resistance is a significant challenge in endometrial cancer (EC) treatment.
- Epidermal growth factor receptor (EGFR) signaling is implicated in various cancers, potentially influencing hormone resistance.
Purpose of the Study:
- To investigate the role of gefitinib in overcoming progestin resistance in a human endometrial carcinoma xenograft model.
- To evaluate the effect of EGFR overexpression on progestin resistance and the efficacy of gefitinib therapy.
Main Methods:
- Established a progestin-resistant Ishikawa endometrial cancer cell line (Ishikawa-pLWERNL) with stable EGFR overexpression.
- Utilized xenografts in BALB/c nude mice, treating with gefitinib alone or combined with medroxyprogesterone acetate (MPA).
- Analyzed EGFR and progesterone receptor isoform B (PR-B) expression via Western blot and immunohistochemistry; investigated EGFR signaling pathway inhibition.
Main Results:
- Progestin-resistant xenografts exhibited higher EGFR and lower PR-B expression compared to sensitive ones.
- EGFR overexpression correlated with reduced progestin sensitivity, decreased PR-B, and activated downstream signaling.
- Gefitinib effectively inhibited proliferation and reversed progestin resistance in EGFR-overexpressing EC xenografts.
Conclusions:
- The developed in vivo model is valuable for studying EGFR and progestin resistance interactions in EC.
- Gefitinib demonstrates potential as a therapeutic agent for progestin-resistant endometrial cancer.
