Krüppel-like factor 8 is a novel androgen receptor co-activator in human prostate cancer
| العنوان: | Krüppel-like factor 8 is a novel androgen receptor co-activator in human prostate cancer |
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| المؤلفون: | Yu Su, Xiao-min Wang, Xue-feng Gu, De-jun Yang, Wan-Hai Xu, Hong-jiang He |
| المصدر: | Acta Pharmacologica Sinica. 34:282-288 |
| بيانات النشر: | Springer Science and Business Media LLC, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Male, Transcriptional Activation, medicine.medical_specialty, Kruppel-Like Transcription Factors, Mice, Nude, urologic and male genital diseases, Small hairpin RNA, Mice, Prostate cancer, Nude mouse, Cell Line, Tumor, Internal medicine, LNCaP, medicine, Animals, Humans, Pharmacology (medical), MTT assay, Cell Proliferation, Pharmacology, biology, Cell growth, business.industry, Prostate, Prostatic Neoplasms, General Medicine, Transfection, medicine.disease, biology.organism_classification, Gene Expression Regulation, Neoplastic, Repressor Proteins, Androgen receptor, Endocrinology, Receptors, Androgen, Cancer research, Original Article, business, Protein Binding |
| الوصف: | Kruppel-like factor 8 (KLF8) plays important roles in cell cycle and oncogenic transformation. On other hand, androgen receptor (AR) is crucial in development of both androgen-dependent and independent prostatic malignancies. The aim of this study is to investigate the role of KLF8 in prostate cancer (PCa) and the relationship between KLF8 and AR. Eight human PCa cell lines, including androgen-dependent LNCap cells and androgen-independent 22Rv1 cells, as well as human PCa samples were studied. LNCap cells and 22Rv1 cells were transfected with plasmids encoding full-length wild-type KLF8 or KLF8 shRNA. The expression of KLF8 protein was detected using Western blotting or immunohistochemical staining. Cell proliferation in vitro was measured with MTT assay, and in vivo in a xenograft nude mouse model. Yeast two-hybrid screening, co-immunoprecipitation and pull down assays were used to examine the binding of KLF8 to AR. Luciferase reporter gene assay was used to measure the transcriptional activity of the genes targeted by AR. In 133 human PCa samples, KLF8 protein staining was observed in 92.65% (63/68) of high-grade PCa, 66.15% (43/65) of low-grade PCa, and 6.82% (3/44) of adjacent normal tissues. The expression of KLF8 was significantly associated with poorer overall survival. Overexpression of KLF8 enhanced the proliferation of both LNCap and 22Rv1 cells, while knockdown of endogenous KLF8 suppressed the proliferation. These manipulations exerted similar effects on the tumor volumes in the xenograft nude mouse model. Yeast two-hybrid screening revealed that KLF8 was a novel AR-interacting protein. With pull down assay and co-immunoprecipitation assay, we demonstrated that KLF8 bound directly to AR, and KLF8 enhanced AR target gene transcription. The results demonstrate that KLF8 is a novel AR transcriptional co-activator that is overexpressed in PCa and may play a role in progression of hormone-refractory PCa. |
| تدمد: | 1745-7254 1671-4083 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::46907730b9fbbf1f49bbe1256f6b1154 https://doi.org/10.1038/aps.2012.130 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....46907730b9fbbf1f49bbe1256f6b1154 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17457254 16714083 |
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