Flightless I Homolog Represses Prostate Cancer Progression through Targeting Androgen Receptor Signaling

前列腺癌 雄激素受体 恩扎鲁胺 基因敲除 癌症研究 生物 交易激励 癌症 基因表达 细胞凋亡 基因 遗传学
作者
Tao Wang,Wen Song,Yuan Chen,Ruibao Chen,Zhuo Liu,Licheng Wu,Mingchao Li,Jun Yang,Liang Wang,Jihong Liu,Zhangqun Ye,Chenguang Wang,Ke Chen
出处
期刊:Clinical Cancer Research [American Association for Cancer Research]
卷期号:22 (6): 1531-1544 被引量:29
标识
DOI:10.1158/1078-0432.ccr-15-1632
摘要

Abstract Purpose: Flightless I (FLII), member of the gelsolin superfamily of actin-remodeling proteins, functions as a transcriptional coregulator. We aim to evaluate a tumor-suppressive function of FLII in regulating androgen receptor (AR) in prostate cancer progression. Experimental Design: We examined FLII protein and mRNA expression in clinical prostate cancer specimens by immunohistochemistry. Kaplan–Meier analysis was conducted to evaluate the difference in disease-overall survival associated with the expression levels of FLII and AR. Prostate cancer cells stably expressing FLII or shRNA knockdown were used for functional analyses. Immunoprecipitation, Luciferase reporter, and immunofluorescence staining assays were performed to examine the functional interaction between FLII and AR. Results: Our analysis of the expression levels of FLII in a clinical gene expression array dataset showed that the expression of FLII was positively correlated with the overall survival of prostate cancer patients exhibiting high levels of AR expression. Examination of protein and mRNA levels of FLII showed a significant decrease of FLII expression in human prostate cancers. AR and FLII formed a complex in a ligand-dependent manner through the ligand-binding domain (LBD) of AR. Subsequently, we observed a competitive binding to AR between FLII and the ligand. FLII inhibited AR transactivation and decreased AR nuclear localization. Furthermore, FLII contributed to castration-sensitive and castration-resistant prostate cancer cell growth through AR-dependent signaling, and reintroduction of FLII in prostate cancer cells sensitized the cells to bicalutamide and enzalutamide treatment. Conclusions: FLII plays a tumor-suppressive role and serves as a crucial determinant of resistance of prostate cancer to endocrine therapies. Clin Cancer Res; 22(6); 1531–44. ©2015 AACR.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
1秒前
1秒前
大红先生完成签到,获得积分10
1秒前
华仔应助可乐采纳,获得30
1秒前
美丽万怨完成签到,获得积分10
2秒前
Jasper应助arya采纳,获得10
2秒前
2秒前
3秒前
皮皮怪完成签到,获得积分10
3秒前
南辞完成签到,获得积分20
3秒前
Elijah完成签到 ,获得积分10
4秒前
坚强的秋尽完成签到,获得积分10
4秒前
壮观的裙子完成签到,获得积分20
5秒前
5秒前
6秒前
领导范儿应助yy采纳,获得10
6秒前
zm发布了新的文献求助10
6秒前
小二郎应助Salamenda采纳,获得10
7秒前
mumu发布了新的文献求助30
7秒前
7秒前
lee发布了新的文献求助20
8秒前
研友_VZG7GZ应助阔达幻丝采纳,获得30
9秒前
南辞发布了新的文献求助20
9秒前
9秒前
温柔可乐完成签到,获得积分10
9秒前
uo完成签到,获得积分10
10秒前
思源应助威武鸽子采纳,获得10
10秒前
羽翼发布了新的文献求助10
10秒前
11秒前
11秒前
轻松博超发布了新的文献求助10
11秒前
12秒前
12秒前
彳亍1117应助无语的惜芹采纳,获得20
12秒前
自由绿蓉发布了新的文献求助10
13秒前
科研通AI5应助阿虎采纳,获得10
13秒前
等待冬亦应助keflgfdm采纳,获得20
15秒前
Trinity发布了新的文献求助10
16秒前
科研通AI5应助caiwenwen采纳,获得10
18秒前
buling发布了新的文献求助10
18秒前
高分求助中
Thinking Small and Large 500
Algorithmic Mathematics in Machine Learning 500
Mapping the Stars: Celebrity, Metonymy, and the Networked Politics of Identity 400
Single Element Semiconductors: Properties and Devices 300
Getting Published in SSCI Journals: 200+ Questions and Answers for Absolute Beginners 300
Parallel Optimization 200
Deciphering Earth's History: the Practice of Stratigraphy 200
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 物理 生物化学 纳米技术 计算机科学 化学工程 内科学 复合材料 物理化学 电极 遗传学 量子力学 基因 冶金 催化作用
热门帖子
关注 科研通微信公众号,转发送积分 3835479
求助须知:如何正确求助?哪些是违规求助? 3377803
关于积分的说明 10500774
捐赠科研通 3097386
什么是DOI,文献DOI怎么找? 1705784
邀请新用户注册赠送积分活动 820705
科研通“疑难数据库(出版商)”最低求助积分说明 772219