| Summary: | 博士 === 國立臺灣大學 === 生化科學研究所 === 102 === Adenomyosis, endometrial hyperplasia and endometriosis are the most common gynecological disorders that result from the abnormal growth of the endometrium. Adenomyosis is associated with benign lesions, but endometrial hyperplasia is a high-risk disease and is considered to be a precursor of endometrial carcinoma. Endometriosis is not only related to ovarian cancer but is also highly associated with other cancers. The pathogenesis of these disorders is associated with gene regulation. LCN2 is a member of the lipocalin family and is also a kind of acute-phase protein. Estrogen can induce the secretion of LCN2 protein in the endometrium during the menstrual cycle. Stress, such as cellular starvation, may also cause the production of LCN2 protein. LCN2 has the ability to elicit or inhibit the process of apoptosis under different conditions.
Two major topics were investigated in this study. The first was the relationship between the protein expression level of LCN2 and the epithelial-mesenchymal transition (EMT) in adenomyosis and endometrial hyperplasia. Next, according to the relativity, functional characterization of LCN2 during the initial endometriosis was verified.
Analysis of the mRNA and protein expression level of LCN2 and other cancer-related genes in adenomyosis and endometrial hyperplasia showed that LCN2 expression was significantly higher in endometrial hyperplasia. Furthermore, via immunohistochemistry, the overexpression of LCN2 protein in the glandular epithelial cells but not the stroma cells in endometrial hyperplasia was confirmed. The expression pattern of LCN2 correlated positively with cyclooxygenase 2 (COX2) and CDH1 and negatively with vimentin and CTNNB1. This suggests that the increased LCN2 expression in patients with endometrial hyperplasia may participate in the prevention of the transition from hyperplasia to carcinoma.
The animal model was used to verify the possible role of LCN2 in these endometrial disorders. Compared to adenomyosis and endometrial hyperplasia, the animal model of endometriosis is easier to establish. Autotransplantation of mouse endometrial tissue into the peritoneum was used as an animal model to analyze the Lcn2 protein expression level in the blood, peritoneal fluid and ectopic tissues during the pathogenesis of endometriosis and to study the cellular behavior in primary mouse endometrial epithelium cells affected by Lcn2 protein. The role of LCN2 in the pathology of endometriosis was investigated. The growth of ectopic endometrial tissue was inhibited by the Lcn2 antibodies in mice with implanted endometrial tissue. The increase of EMT, cellular migration and invasion ability correlated with the up-regulation of LCN2 expression in primary endometrial epithelial cells under the influence of nutrient deprivation. Our results reveal that LCN2 is highly related to endometriosis and might be involved in the formation of endometriosis tissues. This suggests that LCN2 could be a potential biomarker and target for clinical therapy in treating hyperplasia and endometriosis.
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