Characterization of HCI-EC-23 a novel estrogen- and progesterone-responsive endometrial cancer cell line

Craig M. Rush; Zannel Blanchard; Jacob T. Polaski; Kyle S. Osborne; Krystle Osby; Jeffery M. Vahrenkamp; Chieh-Hsiang Yang; David H. Lum; Christy R. Hagan; Kimberly K. Leslie; Miles A. Pufall; Kristina W. Thiel; Jason Gertz

doi:10.1038/s41598-022-24211-8

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Characterization of HCI-EC-23 a novel estrogen- and progesterone-responsive endometrial cancer cell line

Journal article

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Characterization of HCI-EC-23 a novel estrogen- and progesterone-responsive endometrial cancer cell line

Craig M. Rush, Zannel Blanchard, Jacob T. Polaski, Kyle S. Osborne, Krystle Osby, Jeffery M. Vahrenkamp, Chieh-Hsiang Yang, David H. Lum, Christy R. Hagan, Kimberly K. Leslie, …

Scientific reports, Vol.12(1), pp.1-17

11/17/2022

DOI: 10.1038/s41598-022-24211-8

PMCID: PMC9672046

PMID: 36396974

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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.

Endometrial Cancer

Epigenetics

Cancer genomics

Cancer models

Transcriptomics

Details

Title: Subtitle: Characterization of HCI-EC-23 a novel estrogen- and progesterone-responsive endometrial cancer cell line
Creators: Craig M. Rush - University of Utah
Zannel Blanchard - Salt Lake City, UT USA
Jacob T. Polaski - Salt Lake City, UT USA
Kyle S. Osborne - Salt Lake City, UT USA
Krystle Osby - Salt Lake City, UT USA
Jeffery M. Vahrenkamp - Salt Lake City, UT USA
Chieh-Hsiang Yang - Salt Lake City, UT USA
David H. Lum - Salt Lake City, UT USA
Christy R. Hagan - Kansas City, KS USA
Kimberly K. Leslie - Albuquerque, NM USA
Miles A. Pufall - Iowa City, IA USA
Kristina W. Thiel - Iowa City, IA USA
Jason Gertz - Salt Lake City, UT USA
Resource Type: Journal article
Publication Details: Scientific reports, Vol.12(1), pp.1-17
DOI: 10.1038/s41598-022-24211-8
PMID: 36396974
PMCID: PMC9672046
NLM abbreviation: Sci Rep
eISSN: 2045-2322
Publisher: Nature Publishing Group UK
Grant note: T32 HG008962; R01 HG008974S1; R01 HG008974 / ;
Language: English
Date published: 11/17/2022
Academic Unit: Obstetrics and Gynecology; Biochemistry and Molecular Biology
Record Identifier: 9984318359702771

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