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A novel human endometrial epithelial cell line for modeling gynecological diseases and for drug screening.

Publication ,  Journal Article
Park, Y; Jung, J-G; Yu, Z-C; Asaka, R; Shen, W; Wang, Y; Jung, W-H; Tomaszewski, A; Shimberg, G; Chen, Y; Parimi, V; Gaillard, S; Shih, I-M; Wang, T-L
Published in: Lab Invest
November 2021

Endometrium-related malignancies including uterine endometrioid carcinoma, ovarian clear cell carcinoma and ovarian endometrioid carcinoma are major types of gynecologic cancer, claiming more than 13,000 women's lives annually in the United States. In vitro cell models that recapitulate "normal" endometrial epithelial cells and their malignant counterparts are critically needed to facilitate the studies of pathogenesis in endometrium-related carcinomas. To achieve this objective, we have established a human endometrial epithelial cell line, hEM3, through immortalization and clonal selection from a primary human endometrium culture. hEM3 exhibits stable growth in vitro without senescence. hEM3 expresses protein markers characteristic of the endometrial epithelium, and they include PAX8, EpCAM, cytokeratin 7/8, and ER. hEM3 does not harbor pathogenic germline mutations in genes involving DNA mismatch repair (MMR) or homologous repair (HR) pathways. Despite its unlimited capacity of in vitro proliferation, hEM3 cells are not transformed, as they are not tumorigenic in immunocompromised mice. The cell line is amenable for gene editing, and we have established several gene-specific knockout clones targeting ARID1A, a tumor suppressor gene involved in the SWI/SNF chromatin remodeling. Drug screening demonstrates that both HDAC inhibitor and PARP inhibitor are effective in targeting cells with ARID1A deletion. Together, our data support the potential of hEM3 as a cell line model for studying the pathobiology of endometrium-related diseases and for developing effective precision therapies.

Duke Scholars

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Published In

Lab Invest

DOI

EISSN

1530-0307

Publication Date

November 2021

Volume

101

Issue

11

Start / End Page

1505 / 1512

Location

United States

Related Subject Headings

  • Receptors, Estrogen
  • Pathology
  • Mice
  • Humans
  • Female
  • Epithelial Cells
  • Endometrium
  • Drug Evaluation, Preclinical
  • Cell Line
  • Animals
 

Citation

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Park, Y., Jung, J.-G., Yu, Z.-C., Asaka, R., Shen, W., Wang, Y., … Wang, T.-L. (2021). A novel human endometrial epithelial cell line for modeling gynecological diseases and for drug screening. Lab Invest, 101(11), 1505–1512. https://doi.org/10.1038/s41374-021-00624-3
Park, Youngran, Jin-Gyoung Jung, Zheng-Cheng Yu, Ryoichi Asaka, Wenjing Shen, Yeh Wang, Wei-Hung Jung, et al. “A novel human endometrial epithelial cell line for modeling gynecological diseases and for drug screening.Lab Invest 101, no. 11 (November 2021): 1505–12. https://doi.org/10.1038/s41374-021-00624-3.
Park Y, Jung J-G, Yu Z-C, Asaka R, Shen W, Wang Y, et al. A novel human endometrial epithelial cell line for modeling gynecological diseases and for drug screening. Lab Invest. 2021 Nov;101(11):1505–12.
Park, Youngran, et al. “A novel human endometrial epithelial cell line for modeling gynecological diseases and for drug screening.Lab Invest, vol. 101, no. 11, Nov. 2021, pp. 1505–12. Pubmed, doi:10.1038/s41374-021-00624-3.
Park Y, Jung J-G, Yu Z-C, Asaka R, Shen W, Wang Y, Jung W-H, Tomaszewski A, Shimberg G, Chen Y, Parimi V, Gaillard S, Shih I-M, Wang T-L. A novel human endometrial epithelial cell line for modeling gynecological diseases and for drug screening. Lab Invest. 2021 Nov;101(11):1505–1512.

Published In

Lab Invest

DOI

EISSN

1530-0307

Publication Date

November 2021

Volume

101

Issue

11

Start / End Page

1505 / 1512

Location

United States

Related Subject Headings

  • Receptors, Estrogen
  • Pathology
  • Mice
  • Humans
  • Female
  • Epithelial Cells
  • Endometrium
  • Drug Evaluation, Preclinical
  • Cell Line
  • Animals