Establishment of a Novel In Vitro Model of Endometriosis with Oncogenic and Mutations for Understanding the Underlying Biology and Molecular Pathogenesis.

Endometriosis-harboring cancer-associated somatic mutations of and provides new opportunities for studying the multistep processes responsible for the functional and molecular changes in this disease. We aimed to establish a novel in vitro endometriosis model to clarify the functional behavior and molecular pathogenesis of this disorder. Immortalized HMOsisEC10 human ovarian endometriotic epithelial cell line was used in which and mutations were introduced. Migration, invasion, proliferation, and microarray analyses were performed using and mutant cell lines. In vitro assays showed that migration, invasion, and proliferation were significantly increased in and mutant cell lines, indicating that these mutations played causative roles in the aggressive behavior of endometriosis. Microarray analysis identified a cluster of gene signatures; among them, two significantly upregulated cancer-related genes, lysyl oxidase () and pentraxin3 (), were associated with cell proliferation, invasion, and migration capabilities. Furthermore, siRNA knockdown of the two genes markedly reduced the metastatic ability of the cells. These results suggest that endometriosis with or mutations can significantly enhance cell migration, invasion, and proliferation by upregulating and . We propose that and silencing using small molecules could be an alternative therapeutic regimen for severe endometriosis.