1. Gli2 mediates the development of castration‑resistant prostate cancer
- Author
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Lu-Zhe Sun, Carla Zeballos, Hakim Bouamar, Peter J. Houghton, Xiang Gu, Tai Qin, Yuhui Wang, Lu Xia, Junhua Yang, Bingzhi Wang, You Zhou, Weishe Zhang, and Haiyan Zhu
- Subjects
Male ,0301 basic medicine ,Cancer Research ,animal structures ,Cell Survival ,Antineoplastic Agents ,Zinc Finger Protein Gli2 ,Biology ,urologic and male genital diseases ,Tosyl Compounds ,Small hairpin RNA ,Mice ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,mouse xenograft ,Cell Line, Tumor ,Nitriles ,LNCaP ,medicine ,Animals ,Humans ,castration-resistant prostate cancer ,Anilides ,RNA, Small Interfering ,Gene knockdown ,Oncogene ,Nuclear Proteins ,Cancer ,Androgen Antagonists ,Articles ,Cell cycle ,prostate cancer ,medicine.disease ,Xenograft Model Antitumor Assays ,hedgehog signaling ,Hedgehog signaling pathway ,Gene Expression Regulation, Neoplastic ,Prostatic Neoplasms, Castration-Resistant ,Cell Transformation, Neoplastic ,030104 developmental biology ,Oncology ,Gene Knockdown Techniques ,030220 oncology & carcinogenesis ,Disease Progression ,Cancer research ,glioma-associated oncogene family zinc finger 2 - Abstract
Glioma-associated oncogene family zinc finger 2 (Gli2), a key component of the hedgehog signaling pathway, has been previously demonstrated to promote the malignant properties of prostate cancer in vitro. However, the role of Gli2 in the development of castration-resistant prostate cancer (CRPC) has yet to be fully elucidated. In the present study, Gli2 expression was knocked down in androgen-responsive prostate cancer cells using an inducible Gli2 short hairpin RNA. Suppression of Gli2 expression resulted in significant reduction of cell viability, increased the proportion of cells in the G0/G1 phases of the cell cycle and reduced the expression of genes associated with cell cycle progression. Gli2 knockdown sensitized both androgen-dependent and -independent prostate cancer cells to the antiandrogen drug Casodex and prevented the outgrowth of LNCaP prostate cancer cells. In addition, Gli2 knockdown significantly suppressed the development of CRPC in a LNCaP xenograft mouse model, which was reversed by the re-expression of Gli2. In conclusion, to the best of our knowledge, the present study was the first occasion in which the essential role of Gli2 in the development of CRPC was demonstrated, providing a potential therapeutic target for the intervention of CRPC.
- Published
- 2020
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