Endometrial hyperplasia with loss of APC in a novel population of Lyz2-expressing mouse endometrial epithelial cells.
Endometrial hyperplasia with loss of APC in a novel population of Lyz2-expressing mouse endometrial epithelial cells.
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DOI：
10.1093/carcin/bgac101
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发表时间：
2023-05-15
期刊：
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
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作者：
APC的杂合性缺失和启动子超甲基化在人类子宫内膜癌中经常观察到，子宫内膜癌是美国最常见的妇科癌症，但其在子宫内膜上皮中的致癌驱动状态尚未得到证实。我们已经确定了一个新的人口的祖子宫内膜上皮细胞（EECs）的小鼠表达溶菌酶M（LysM），并产生约15%的所有EECs在成年小鼠。LysM是一种糖苷水解酶，由Lyz 2编码，作为先天免疫系统的一部分，其功能是保护细胞免受细菌的侵害。它的表达已被证明在造血干细胞的子集和专门的肺和小肠上皮细胞。与野生型小鼠相比，LysM + EECs中Apc的条件性缺失导致显著更多的上皮细胞。在5月龄时，ApccKO小鼠具有增大的子宫角，病理学与子宫内膜增生一致，具有囊性子宫内膜腺、非绒毛状腔乳头和核乳头。在ApccKO小鼠的EEC中观察到β-连环蛋白和ERα的核蓄积，这两种蛋白均已知可诱导子宫内膜增生。这些结果证实，APC在EECs中的损失可导致类似于子宫内膜增生的表型。
Loss of heterozygosity and promoter hypermethylation of APC is frequently observed in human endometrial cancer, which is the most common gynecological cancer in the USA, but its carcinogenic driver status in the endometrial epithelium has not been confirmed. We have identified a novel population of progenitor endometrial epithelial cells (EECs) in mice that express lysozyme M (LysM) and give rise to approximately 15% of all EECs in adult mice. LysM is a glycoside hydrolase that is encoded by Lyz2 and functions to protect cells from bacteria as part of the innate immune system. Its expression has been shown in a subset of hematopoietic stem cells and in specialized lung and small intestinal epithelial cells. Conditional deletion of Apc in LysM + EECs results in significantly more epithelial cells compared to wild-type mice. At 5 months of age, the ApccKO mice have enlarged uterine horns with pathology that is consistent with endometrial hyperplasia with cystic endometrial glands, non-villous luminal papillae and nuclear atypia. Nuclear accumulation of β-catenin and ERα, both of which are known to induce endometrial hyperplasia, was observed in the EECs of the ApccKO mice. These results confirm that loss of APC in EECs can result in a phenotype similar to endometrial hyperplasia.
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影响因子：
11.2
作者：
Kim TH;Lee DK;Cho SN;Orvis GD;Behringer RR;Lydon JP;Ku BJ;McCampbell AS;Broaddus RR;Jeong JW
通讯作者：
Jeong JW
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
3
作者：
Clausen, BE;Burkhardt, C;Förster, I
通讯作者：
Förster, I
影响因子：
3.6
作者：
Hayashi, Kanako;Yoshioka, Shin;MacLean, James A., II
通讯作者：
MacLean, James A., II
影响因子：
11.2
作者：
Daikoku T;Hirota Y;Tranguch S;Joshi AR;DeMayo FJ;Lydon JP;Ellenson LH;Dey SK
通讯作者：
Dey SK