Kruppel-like factor 8 is a novel androgen receptor ：o-activator in human prostate cancer

• Published in: 中国药理学报：英文版 no. 2; pp. 282 - 288
• Main Author: Hong-jiang HE Xue-feng GU Wan-hai XU De-jun YANG Xiao-min WANG Yu SU
• Format: Journal Article
• Language: English
• Published: 2013
• Subjects: LNCap细胞; 人类; 免疫共沉淀; 前列腺癌; 活化剂; 生长因子; 细胞恶性转化; 雄激素受体
• ISSN: 1671-4083; 1745-7254

Aim： Kr（Jppel-like factor 8 （KLF8） plays important roles in cell cycle and oncogenic transformation. On other hand, androgen recep- tor （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. Methods Eight human PCa cell lines, including androgen-dependent LNCap cells and androgen-independent 22Rvl cells, as well as human PCa samples were studied. LNCap cells and 22Rvl 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. Results： 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 overa survival. Overexpression of KLF8 enhanced the proliferation of both LNCap and 22Rvl cells, while knockdown of endogenous KLF8 suppressed the proliferation. These manipulations exerted similar effects on the tumor volumes in the xenograft nude mouse mode 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. Conclusion： 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.