ER Expressing Epithelial Endometrial Cancer Cell Line (HCI-EC-23)

The HCI-EC-23 cell line is a novel, adherent endometrioid endometrial cancer (EEC) model that was developed from a patient-derived xenograft (PDX) model. The primary tumor was microsatellite instability-high (MSI-high) and estrogen receptor (ER) positive. The cell line retains these characteristics, maintaining ER expression and estrogen responsiveness both in vitro and in vivo. Characterization of HCI-EC-23 revealed that it is mutated in many commonly altered genes in EEC, such as PTEN, PIK3CA, and ARID1A, and has relatively few copy-number alterations. It exhibits paradoxical activation of ER by tamoxifen and shows an anti-proliferative response to progesterone, which is crucial for translational studies involving synthetic progesterone treatments. In vitro, HCI-EC-23 demonstrates a strong estrogen dependence for proliferation, with estrogen significantly boosting growth and progesterone reducing it. HCI-EC-23 tumors in mice also show estrogen dependence, with a reduction in tumor volume when treated with progesterone. The cell line’s unique features, including its MSI-high status, ER positivity, and distinct genetic background compared to the Ishikawa cell line, make it a valuable model for studying the hormonal underpinnings of endometrial cancer. HCI-EC-23 is well-suited for genetic screens, drug testing, and understanding the molecular aspects of hormonally driven endometrial cancer.