Endometrial hyperplasia with loss of APC in a novel population of Lyz2-expressing mouse endometrial epithelial cells.
Susan M Kitchen-GoosenHeather SchumacherJulie GoodAmanda L PattersonElissa A BoguslawskiRichard A WestBart O WilliamsGalen HostetterDalen W AgnewJose M TeixeiraArthur S AlbertsPublished in: Carcinogenesis (2022)
Loss of heterozygosity and promoter hypermethylation of APC is frequently observed in human endometrial cancer, which is the most common gynecological cancer in the US, 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 LysM and give rise to approximately 15% of all EECs in adult mice. Lysozyme M (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 five months of age, the Apc cKO 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 Apc cKO mice. These results confirm that loss of APC in EECs can result in a phenotype similar to endometrial hyperplasia.
Keyphrases
- endometrial cancer
- wild type
- high fat diet induced
- stem cells
- immune response
- endothelial cells
- type diabetes
- bone marrow
- gene expression
- insulin resistance
- metabolic syndrome
- squamous cell carcinoma
- epithelial mesenchymal transition
- transcription factor
- binding protein
- estrogen receptor
- skeletal muscle
- mesenchymal stem cells
- dna methylation
- signaling pathway
- young adults
- pluripotent stem cells