NDRG2 acts as a negative regulator downstream of androgen receptor and inhibits the growth of androgen-dependent and castration-resistant prostate cancer
| Autor: | Libo Yao, Rui Zhang, Xia Li, Ruixiao Li, Jian Zhang, Yi Zhao, Jing Zhang, Chuigong Yu, Guojun Wu, Jianlin Yuan, Lei Gao, Fan Yang |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Cancer Research medicine.medical_specialty Down-Regulation Gene Expression urologic and male genital diseases Proto-Oncogene Proteins c-myc Mice chemistry.chemical_compound Prostate cancer Castration Resistance Downregulation and upregulation Cell Line Tumor Internal medicine medicine Animals Humans Aged Cell Proliferation Aged 80 and over Pharmacology Cell growth business.industry Tumor Suppressor Proteins Middle Aged medicine.disease Immunohistochemistry Xenograft Model Antitumor Assays Research Papers Tumor Burden Androgen receptor Disease Models Animal Prostatic Neoplasms Castration-Resistant Prostate-specific antigen Castration Endocrinology Oncology chemistry Receptors Androgen Androgens Heterografts Molecular Medicine Signal transduction business Signal Transduction |
| Zdroj: | Cancer Biology & Therapy. 16:287-296 |
| ISSN: | 1555-8576 1538-4047 |
| DOI: | 10.1080/15384047.2014.1002348 |
| Popis: | Castration resistance is a major issue during castration therapy for prostate cancer and thus more effective treatment are needed for castration-resistant prostate cancer (CRPC). NDRG2 (N-Myc downstream regulated gene 2), a recently identified tumor suppressor, was previously shown to inhibit the proliferation and invasion of prostate cancer, but whether NDRG2 is involved in CRPC remains to be known. Because androgen receptor (AR) axis plays an important role in castration resistance, we evaluate the role of NDRG2 in AR signaling and CRPC. Immunohistochemistry examination of prostate cancer tissues demonstrated that the expression of NDRG2 is negatively correlated with that of AR and c-Myc. Furthermore, AR negatively regulates NDRG2, as well as alters levels of c-Myc and prostate specific antigen (PSA). Forced expression of NDRG2 significantly inhibits the in vitro growth of androgen-dependent and castration-resistant prostate cancer cells; this was accompanied by alterations in PSA, but not by those of AR and c-Myc. Finally, by mimicking castration therapy in a xenograft mouse model, we showed that lentivirus-mediated NDRG2 overexpression efficiently overcomes castration resistance. Thus, by acting as a negative regulator downstream of AR, NDRG2 may emerge as a potential therapy molecule for CRPC. |
| Databáze: | OpenAIRE |
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