Abstract
BackgroundEndometrial carcinoma is one of the most common gynecologic malignancies. Estrogen plays a critical role in its pathogenesis, but the underlying mechanism is not clear. Nucleophosmin 1 (NPM1), a multifunctional protein involved in many cellular activities, has been implicated in the tumorigenesis processes. However, the role of NPM1 in endometrial carcinogenesis remains to be elucidated. The present study was aimed to elucidate the role of NPM1 in different clinical stages of human endometrial carcinoma and the underlying mechanism of NPM1 action.MethodsThe distribution and expression of NPM1 in normal endometrium, FIGO stages I to IV endometrial carcinoma tissues was analyzed using immunohistochemistry, RT-qPCR and Western blotting. The association between NPM1 expression and estrogen and estrogen receptor signaling was investigated in primary-cultured FIGO stage I endometrial adenocarcinoma cells.ResultsA strong positive correlation between NPM1 level and the clinical stage and histological grade of endometrial carcinomas was observed. Expression of NPM1 was up-regulated by estrogen in primary-cultured human endometrial adenocarcinoma cells. Furthermore, estrogen increased NPM1 level via estrogen receptor-α (ERα) signaling, nor estrogen receptor-β signaling.ConclusionsExpression of NPM1 was gradually increased with the increase of clinical stages of endometrial carcinomas. Overexpression of NPM1 may play a role in the effects of estrogen on the malignant progression of endometrioid adenocarcinoma via ERα signaling. These findings may extend our understanding of the oncogenesis of steroid hormone-related cancers and have significance for the diagnosis and treatment of this carcinoma.
Highlights
Endometrial carcinoma is one of the most common gynecologic malignancies
Expression of Nucleophosmin 1 (NPM1) was up-regulated by estrogen in primary-cultured human endometrial adenocarcinoma cells To investigate if there is a possible hormonal regulation of NPM1 expression, we quantified NPM1 expression levels in primary-cultured Federation of Gynecology and Obstetrics (FIGO) stages I endometrial adenocarcinoma cells stimulated with estrogen (E2 0, 0.1, 0.5, 1, 5 μm/ml) for 24 h using qRT-PCR and Western blotting
We investigated whether the estrogenregulated NPM1 expression was correlated with estrogen receptor-α in the primary-cultured FIGO stages I human endometrial adenocarcinoma cells
Summary
Endometrial carcinoma is one of the most common gynecologic malignancies. Estrogen plays a critical role in its pathogenesis, but the underlying mechanism is not clear. The present study was aimed to elucidate the role of NPM1 in different clinical stages of human endometrial carcinoma and the underlying mechanism of NPM1 action. NPM1 has proved to be a multifunctional protein that is involved in various cellular activities, including transport of preribosomal particles and ribosome biogenesis [11], centrosome duplication [12,13], response to stress-stimuli [14,15], regulation of DNA transcription, maintenance of genomic stability and embryonic development [16], which suggests a role for NPM1 in tumorigenesis. The alteration of NPM1 in human cancer (through overexpression or genetic modification) indicates that NPM1 might play a role as both an oncogene and a tumor suppressor, depending on its dosage and level of expression [25]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
