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Inhibiting 3ßHSD1 to eliminate the oncogenic effects of progesterone in prostate cancer.
Hou, Zemin; Huang, Shengsong; Mei, Zejie; Chen, Longlong; Guo, Jiacheng; Gao, Yuanyuan; Zhuang, Qian; Zhang, Xuebin; Tan, Qilong; Yang, Tao; Liu, Ying; Chi, Yongnan; Qi, Lifengrong; Jiang, Ting; Shao, Xuefeng; Wu, Yan; Xu, Xiaojun; Qin, Jun; Ren, Ruobing; Tang, Huiru; Wu, Denglong; Li, Zhenfei.
Afiliación
  • Hou Z; State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
  • Huang S; Department of Urology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China.
  • Mei Z; State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
  • Chen L; State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Metabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular Phenomics, Zhongshan Hospital, Fudan University, Shanghai 200438, China.
  • Guo J; CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
  • Gao Y; State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
  • Zhuang Q; State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
  • Zhang X; State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
  • Tan Q; State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
  • Yang T; Department of Urology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China.
  • Liu Y; Department of Urology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China.
  • Chi Y; Department of Urology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China.
  • Qi L; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu, China.
  • Jiang T; Department of Urology, First People's Hospital of Taicang, Taicang, Jiangsu 215400, China.
  • Shao X; Department of Urology, First People's Hospital of Taicang, Taicang, Jiangsu 215400, China.
  • Wu Y; Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China.
  • Xu X; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu, China.
  • Qin J; CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
  • Ren R; Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China.
  • Tang H; Kobilka Institute of Innovative Drug Discovery, School of Life and Health Sciences, the Chinese University of Hong Kong, Shenzhen, Guangdong 518172, China.
  • Wu D; State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Metabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular Phenomics, Zhongshan Hospital, Fudan University, Shanghai 200438, China.
  • Li Z; Department of Urology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China.
Cell Rep Med ; 3(3): 100561, 2022 03 15.
Article en En | MEDLINE | ID: mdl-35492874
ABSTRACT
Prostate cancer continuously progresses following deprivation of circulating androgens originating from the testis and adrenal glands, indicating the existence of oncometabolites beyond androgens. In this study, mass-spectrometry-based screening of clinical specimens and a retrospective analysis on the clinical data of prostate cancer patients indicate the potential oncogenic effects of progesterone in patients. High doses of progesterone activate canonical and non-canonical androgen receptor (AR) target genes. Physiological levels of progesterone facilitate cell proliferation via GATA2. Inhibitors of 3ß-hydroxysteroid dehydrogenase 1 (3ßHSD1) has been discovered and shown to suppress the generation of progesterone, eliminating its transient and accumulating oncogenic effects. An increase in progesterone is associated with poor clinical outcomes in patients and may be used as a predictive biomarker. Overall, we demonstrate that progesterone acts as an oncogenic hormone in prostate cancer, and strategies to eliminate its oncogenic effects may benefit prostate cancer patients.
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Texto completo: 1 Colección: 01-internacional Asunto principal: Neoplasias de la Próstata / Andrógenos Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans / Male Idioma: En Revista: Cell Rep Med Año: 2022 Tipo del documento: Article País de afiliación: China
Texto completo
Imprimir
XML
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Buscar en Google

Texto completo: 1 Colección: 01-internacional Asunto principal: Neoplasias de la Próstata / Andrógenos Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans / Male Idioma: En Revista: Cell Rep Med Año: 2022 Tipo del documento: Article País de afiliación: China