Dissertation/ Thesis
The Pathophysiology Roles of Androgen Receptor in Endometrial Cancer
| العنوان: | The Pathophysiology Roles of Androgen Receptor in Endometrial Cancer |
|---|---|
| Alternate Title: | 雄性激素受體在子宮內膜癌病理生理之探討 |
| المؤلفون: | Lu-min Chen, 陳璐敏 |
| Thesis Advisors: | Wen-Lung Ma, 馬文隆 |
| سنة النشر: | 2018 |
| المجموعة: | National Digital Library of Theses and Dissertations in Taiwan |
| الوصف: | 106 Purpose: Endometrial cancer is sex steroid hormones-related female malignancy. Androgen and androgen receptor (AR) signals have been implicated in endometrial cancer progression. Cancer stem/progenitor cells (CSPC) are suspected linking to chemoresistance in endometrial cancer patients. The AR poly-glutamine polymorphism (AR-Q) was reported to play role in endometrial cancer development. In this study we investigate AR is associated with chemoresistance in endometrial cancer patient via increase CD133 and AR-Q associated with endometrial cancer patients prognosis by interplay with aryl hydrocarbon receptor (AhR) Experimental Design: To investigate the AR role in endometrial cancer cell stemness which is related to cisplatin resistance. Ishikawa endometrial cancer cells (high CD133+ expressing cells) were introduced in this study, transfected AR cDNA in the Ishikawa endometrial cancer cells. For AR-Q study, Specimens analyzed were obtained from patients diagnosed with endometrial cancer from 2003 to 2006 at the China Medical University (Taichung, Taiwan), analyzing patient AR-Q polymorphism and AhR expressions. In vitro study, activity of androgen-response element (ARE) and dioxin-responsive element (DRE) with AR-Qs length (Q13 > Q25 > Q35) was compared. Results: We found AR expression increased na??ve endometrial cancer side/population (S/P), CSPC population, cell migration, and epithelial- mesenchymal transition (EMT). Meanwhile, it decreased cisplatin cytotoxic effect on endometrial cells. We also found overall survival benefit is ascending with AR-Q lengths (5-year OS of 61.3% in Q length < 20 and 88% in Q length > 23). AhR is higher expressed in short AR-Q tumor compared to that in long AR-Q patient. In vitro study found ARE activity descends with AR-Qs length (Q13 > Q25 > Q35), while BaP suppresses ARE activities in endometrial cancer cells. Furthermore, AR-Q13 (but not AR-Q25, or -35) enhances BaP-induced DRE activity. Conclusions: The results indicate that androgen/AR signal could promote endometrial cancer basal CSPC levels. While cancer cells upfront cisplatin treatments, AR might further enhance cells resistance to therapy via increasing CSPC. Also we show that shorter AR-Q has poorer endometrial cancer prognosis. This phenomenon is reversely correlated to AhR expression. |
| Original Identifier: | 106CMCH5521012 |
| نوع الوثيقة: | 學位論文 ; thesis |
| وصف الملف: | 74 |
| الاتاحة: | http://ndltd.ncl.edu.tw/handle/49h4d6 |
| رقم الانضمام: | edsndl.TW.106CMCH5521012 |
| قاعدة البيانات: | Networked Digital Library of Theses & Dissertations |
| الوصف غير متاح. |