| RRC ID |
77101
|
| 著者 |
Rush CM, Blanchard Z, Polaski JT, Osborne KS, Osby K, Vahrenkamp JM, Yang CH, Lum DH, Hagan CR, Leslie KK, Pufall MA, Thiel KW, Gertz J.
|
| タイトル |
Characterization of HCI-EC-23 a novel estrogen- and progesterone-responsive endometrial cancer cell line.
|
| ジャーナル |
Sci Rep
|
| Abstract |
Most endometrial cancers express the hormone receptor estrogen receptor alpha (ER) and are driven by excess estrogen signaling. However, 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 estrogen 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 strongly reduced upon combination estrogen and progesterone treatment. HCI-EC-23 exhibits strong estrogen dependence for tumor growth in vivo and tumor size is reduced by combination estrogen and progesterone treatment. Molecular characterization of estrogen 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 an estrogen- and progesterone-responsive cell line model that can be used to study the hormonal aspects of endometrial cancer.
|
| 巻・号 |
12(1)
|
| ページ |
19731
|
| 公開日 |
2022-11-17
|
| DOI |
10.1038/s41598-022-24211-8
|
| PII |
10.1038/s41598-022-24211-8
|
| PMID |
36396974
|
| PMC |
PMC9672046
|
| MeSH |
Carcinoma, Endometrioid* / drug therapy
Carcinoma, Endometrioid* / genetics
Cell Line
Endometrial Neoplasms* / drug therapy
Endometrial Neoplasms* / genetics
Endometrial Neoplasms* / metabolism
Estradiol / pharmacology
Estrogens / pharmacology
Estrogens / therapeutic use
Female
Humans
Progesterone / pharmacology
Progesterone / therapeutic use
Tumor Cells, Cultured
|
| IF |
3.998
|
| リソース情報 |
| ヒト・動物細胞 |
JHUAS-1(RCB1544)
JHUEM-2(RCB1551) |
