ABSTRACT
Epithelial-mesenchymal transition (EMT) induced by estrogen contributes to the development of adenomyosis. However, the exact underlying mechanism remains mostly obscure. We hypothesized that a transmembrane glycoprotein neuropilin 1 (NRP1) was critical in the EMT induced by estrogen, accelerating the development of adenomyosis. We firstly investigated the expression pattern of NRP1 in endometrium samples from women with adenomyosis. We found that NRP1 expression was significantly increased in the endometrium of uterine adenomyosis, especially in the ectopic endometrium. To determine the role of NRP1 in the EMT in endometrial cells, we used an NRP1 overexpression retrovirus to up-regulate the NPR1 expression in human endometrial cells (HEC-1-A). Endometrial cells infected with NRP1 retroviruses showed a high expression of NRP1 and exerted a mesenchymal phenotype, characterized by down-regulation of E-cadherin and Occludin, up-regulation of α-SMA and N-cadherin, and enhanced migration. Then, we found that 17ß-estradiol (E2) up-regulated the expression of NRP1 in endometrial cells in a dose-dependent manner, which was eliminated by raloxifene, a selective estrogen receptor inhibitor. Importantly, NRP1 shRNA significantly suppressed the EMT induced by E2 in endometrial cells. And NRP1 shRNA significantly inhibited the phosphorylation of Smad3 and restored the expressions of Slug and Snail1 mRNA. Collectively, these data highlight the possible role of NRP1 in the EMT in the development of adenomyosis and provide a potential therapeutic target for adenomyosis patients.
Subject(s)
Adenomyosis/metabolism , Endometrium/drug effects , Epithelial-Mesenchymal Transition/drug effects , Estradiol/pharmacology , Neuropilin-1/metabolism , Adult , Antigens, CD/metabolism , Cadherins/metabolism , Cell Line , Dose-Response Relationship, Drug , Endometrium/metabolism , Female , Humans , Middle Aged , Snail Family Transcription Factors/metabolism , Up-RegulationABSTRACT
OBJECTIVE: To explore the clinical features, diagnosis, treatment and prognosis of endometrial carcinoma in young, middle-aged and elderly women. METHODS: We retrospectively analyzed the clinical data of 82 cases of endometrial carcinoma in young, middle-aged women and 33 cases of endometrial cacinoma in elderly women. RESULTS: The rates of adenocarcinoma in young, middle-aged and elderly groups were 74.4% and 75.5%, respectively. The young,middle-aged and elderly patients with Stage I endometrial cancer were 64.6% and 69.7%, and those with Stage III and IV were 15.9% and 15.2%, respectively. The histological Grade 1 carcinoma of endometrium in young,middle-aged and elderly women were 70.7% and 60.6%, respectively. The young, middle-aged women without myometrial invasion were more than the elderly women (42.8% vs 15.6%, P < 0.01). The young, middle-aged women with myometrial invasion more than half of myometrial wall were less than the elderly women (10.4% vs 40.6%, P < 0.01). The rate of chemical treatment after the surgery in the elderly women was more than that of the young, middle-aged women (P < 0.05). The 5-year survival rate of the young, middle-aged women was obviously higher than that of the elderly women (92.79% vs 72.21%, P < 0.05). CONCLUSION: Adenocarcinoma and well-differentiated cells are the main pathological characteristics of endometrial carcinoma both in the young, middle-aged and the elderly women. Most young, middle-aged and el-derly patients can be diagnosed and treated in the early stage. Early diagnosis and reasonable treatment can improve the prognosis. The prognosis of the young, middle-aged patients is obviously better than that of the elderly patients, and the myometrial invasion depth may be the main difference.