前列腺癌
LNCaP公司
DU145型
癌症研究
前列腺
转移
癌症
扭曲转录因子
医学
上皮-间质转换
内科学
生物
作者
Wai Kei Kwok,Ming‐Tat Ling,Tak-Wing Lee,Tracy C.M. Lau,Chun Zhou,Xiaomeng Zhang,Chee Wai Chua,Kwok Wah Chan,Franky Leung Chan,Carlotta A. Glackin,Yong-Chuan Wong,Xianghong Wang
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2005-06-15
卷期号:65 (12): 5153-5162
被引量:460
标识
DOI:10.1158/0008-5472.can-04-3785
摘要
Androgen-independent metastatic prostate cancer is the main obstacle in the treatment of this cancer. Unlike a majority of solid cancers, prostate cancer usually shows poor response to chemotherapeutic drugs. In this study, we have shown a potential novel target, TWIST, a highly conserved bHLH transcription factor, in the treatment of prostate cancer. Using malignant and nonmalignant prostate tissues, we found that TWIST expression was highly expressed in the majority (90%) of prostate cancer tissues but only in a small percentage (6.7%) of benign prostate hyperplasia. In addition, the TWIST expression levels were positively correlated with Gleason grading and metastasis, indicating its role in the development and progression of prostate cancer. Furthermore, down-regulation of TWIST through small interfering RNA in androgen-independent prostate cancer cell lines, DU145 and PC3, resulted in increased sensitivity to the anticancer drug taxol-induced cell death which was associated with decreased Bcl/Bax ratio, leading to activation of the apoptosis pathway. More importantly, inactivation of TWIST suppressed migration and invasion abilities of androgen-independent prostate cancer cells, which was correlated with induction of E-cadherin expression as well as morphologic and molecular changes associated with mesenchymal to epithelial transition. These results were further confirmed on the androgen-dependent LNCaP cells ectopically expressing the TWIST protein. Our results have identified TWIST as a critical regulator of prostate cancer cell growth and suggest a potential therapeutic approach to inhibit the growth and metastasis of androgen-independent prostate cancer through inactivation of the TWIST gene.
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