Title: Transactivity alterations of androgen receptor mutants in PC-3 cells of advanced prostate cancers
Abstract:Objective:To study the transactivity alterations of 4 androgen receptor (AR) mutants identified in advanced prostate cancer (PC). Methods: AR (wild-type or mutant) expression vectors, reporter gene pM...Objective:To study the transactivity alterations of 4 androgen receptor (AR) mutants identified in advanced prostate cancer (PC). Methods: AR (wild-type or mutant) expression vectors, reporter gene pMMTV-LUC and pRLSV40-LUC plasmids were cotransfected into PC-3 cells by lipofectamine method. Then the cells were treated with dihydrotestosterone (DHT), estrodial or progesterone for 24 h and were further measured for luciferase activity using a Dual-Luciferase reporter assay system. The expression of AR were detected at protein level by Western blot. Results: Compared with wild-type AR(wtAR), the G142V and D221H variants demonstrated increased transcriptional activities by about 0.3-fold in response to DHT at 2 nmol/L (P0.05). The E872Q variant was more responsive to estradiol and progesterone (2 μmol/L) than to wtAR by 0.27-fold and 0.47-fold, respectively (P0.05). Conclusion: AR gene mutation may cause diverse receptor function characteristics, such as higher transcriptional activities(G142V and D221H) or alteration of ligand specificity(E872Q). These data provide essential information for understanding the roles of AR mutations in the progression of PC.Read More
Publication Year: 2005
Publication Date: 2005-01-01
Language: en
Type: article
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