Up-Regulation of TWIST in Prostate Cancer and Its Implication as a Therapeutic Target
| Autor: | Tracy C.M. Lau, Franky L. Chan, Yong-Chuan Wong, Ming-Tat Ling, Kwok W. Chan, Xiaomeng Zhang, Chun Zhou, Xianghong Wang, Tak-Wing Lee, WK Kwok, Carlotta A. Glackin, Chee Wai Chua |
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| Rok vydání: | 2005 |
| Předmět: |
Male
PCA3 Cancer Research Pathology medicine.medical_specialty Paclitaxel Apoptosis Adenocarcinoma Transfection urologic and male genital diseases Metastasis Mesoderm Twist transcription factor Prostate cancer DU145 Prostate Cell Line Tumor LNCaP Humans Medicine Neoplasm Invasiveness Gene Silencing business.industry Twist-Related Protein 1 Nuclear Proteins Prostatic Neoplasms Cancer Epithelial Cells medicine.disease Up-Regulation Gene Expression Regulation Neoplastic medicine.anatomical_structure Oncology Cancer research business Transcription Factors |
| Zdroj: | Cancer Research. 65:5153-5162 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-04-3785 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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