A novel human endometrial epithelial cell line for modeling gynecological diseases and for drug screening.
A novel human endometrial epithelial cell line for modeling gynecological diseases and for drug screening.
复制标题
一种新的人子宫内膜上皮细胞系，用于妇科疾病的建模和药物筛选。
DOI：
10.1038/s41374-021-00624-3
复制
发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Wang TL
中科院分区：
文献类型：
--
作者：
Park Y;Jung JG;Yu ZC;Asaka R;Shen W;Wang Y;Jung WH;Tomaszewski A;Shimberg G;Chen Y;Parimi V;Gaillard S;Shih IM;Wang TL
子宫内膜相关恶性肿瘤包括子宫内膜样癌、卵巢透明细胞癌和卵巢子宫内膜样癌，是妇科癌症的主要类型，在美国每年夺走1.3万多名妇女的生命。为了便于研究子宫内膜相关癌的发病机制，迫切需要能够概括“正常”子宫内膜上皮细胞及其恶性对应细胞的体外细胞模型。为了实现这一目标，我们从原代人子宫内膜培养物中通过永生化和克隆选择建立了人子宫内膜上皮细胞系hEM3。HEM3在体外生长稳定，不衰老。HEM3表达子宫内膜上皮特有的蛋白标记物，包括PAX8、EpCAM、细胞角蛋白7/8和ER。HEM3在涉及DNA错配修复(MMR)或同源修复(HR)途径的基因中不存在致病胚系突变。尽管hEM3细胞在体外具有无限的增殖能力，但它不会转化，因为它们在免疫受损的小鼠身上不会产生肿瘤。该细胞系可以进行基因编辑，我们已经建立了几个针对ARID1A的基因特异性敲除克隆，ARID1A是一种参与SWI/SNF染色质重塑的肿瘤抑制基因。药物筛选表明，HDAC抑制剂和PARP抑制剂均能有效靶向ARID1A缺失的细胞。总之，我们的数据支持hEM3作为研究子宫内膜相关疾病的病理生物学和开发有效的精确治疗方法的细胞系模型的潜力。
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.
登录
查看更多内容
子宫受体适应怀孕的孕激素受体调节。
DOI：
10.1016/j.tem.2018.04.001
发表时间：
2018-07
期刊：
Trends in endocrinology and metabolism: TEM
影响因子：
--
作者：
Wu SP;Li R;DeMayo FJ
通讯作者：
DeMayo FJ
DOI：
10.1056/nejmoa1614814
发表时间：
2017-05-11
期刊：
The New England journal of medicine
影响因子：
--
作者：
Anglesio MS;Papadopoulos N;Ayhan A;Nazeran TM;Noë M;Horlings HM;Lum A;Jones S;Senz J;Seckin T;Ho J;Wu RC;Lac V;Ogawa H;Tessier-Cloutier B;Alhassan R;Wang A;Wang Y;Cohen JD;Wong F;Hasanovic A;Orr N;Zhang M;Popoli M;McMahon W;Wood LD;Mattox A;Allaire C;Segars J;Williams C;Tomasetti C;Boyd N;Kinzler KW;Gilks CB;Diaz L;Wang TL;Vogelstein B;Yong PJ;Huntsman DG;Shih IM
通讯作者：
Shih IM
影响因子：
11.5
作者：
Park, Youngran;Chui, M. Herman;Wang, Tian-Li
通讯作者：
Wang, Tian-Li
影响因子：
10.3
作者：
Guan, Bin;Rahmanto, Yohan Suryo;Shih, Ie-Ming
通讯作者：
Shih, Ie-Ming
影响因子：
28.2
作者：
Shen J;Peng Y;Wei L;Zhang W;Yang L;Lan L;Kapoor P;Ju Z;Mo Q;Shih IeM;Uray IP;Wu X;Brown PH;Shen X;Mills GB;Peng G
通讯作者：
Peng G