GSE210122
Characterization of a novel hormone-responsive endometrial cancer cell line: HCI-EC-23 [ChIP-seq]
Most endometrial cancers are driven by excess estrogen signaling and express the hormone receptor estrogen receptor alpha (ER). Evaluation of the estrogen response in endometrial cancer cells has been limited by the availability of hormonally responsive in vitro models, with one cell line, Ishikawa, being used in most studies. Here, we describe a novel, adherent endometrioid endometrial cancer (EEC) cell line model, HCI-EC-23. We show that HCI-EC-23 retains ER expression and that ER functionally responds to 17b-estradiol (E2) induction over a range of passages. We also demonstrate that this cell line retains paradoxical activation of ER by tamoxifen, which is also observed in Ishikawa and is consistent with clinical data. The mutational landscape shows that HCI-EC-23 is mutated at many of the commonly altered genes in EEC, has relatively few copy-number alterations, and is microsatellite instable high (MSI-high). In vitro proliferation of HCI-EC-23 is modestly enhanced by E2 but is strongly reduced upon combination E2 and progesterone (P4) treatment. HCI-EC-23 exhibit strong E2 dependence for tumor growth in vivo and tumor size is reduced by combination E2 + P4 treatment. Molecular characterization of E2 induction in HCI-EC-23 revealed hundreds of estrogen-responsive genes that significantly overlapped with those regulated in Ishikawa. Analysis of ER genome binding identified similar patterns in HCI-EC-23 and Ishikawa, although ER exhibited more bound sites in Ishikawa. This study demonstrates that HCI-EC-23 is estrogen-responsive and can be used to study the hormonal aspects of endometrial cancer. Overall design: ChIP-seq was used to study genomic binding of estrogen receptor and baseline H3K27ac in the endometrial cancer cell lines HCI-EC-23 and Ishikawa