title: Androgen receptor promotes the oncogenic function of overexpressed Jagged1 in prostate cancer by enhancing cyclin B1 expression via Akt phosphorylation.
abstract: The Jagged1, a Notch signaling pathway ligand, had been shown to have a positive correlation with prostate cancer development. Our study for Jagged1 expression in 218 prostate cancer tissue samples also supports this conclusion. However, the detailed molecular mechanism of Jagged1 in promoting the progression of prostate cancer is still unclear. Through cell proliferation examination, androgen receptor (AR) was found to promote the oncogenic function of Jagged1 to enhance the cell proliferation rate by comparing four prostate cancer cell lines, LNCaP, LAPC4, DU145, and PC3, which was further validated through analyzing the survival of 118 patients treated with androgen-deprivation therapy (ADT) with different expression levels of Jagged1 and AR. More importantly, our data showed that Jagged1 combined with AR could increase the phosphorylation level of Akt and, in turn, phosphorylated Akt plays an important role in regulating the expression level of cyclin B1 by interacting with AR and increasing the transcriptional activity of AR. These data indicate that prostate cancer progression regulated by Jagged1 can be dramatically enhanced by combining with AR through promoting Akt activity.
  
  
  CONCLUSIONS
  This study could benefit our clinical treatments for patients with prostate cancer with overexpressed Jagged1 by targeting AR and Akt.
authors.affiliation: Authors' Affiliations: Departments of Urology.
authors.forename: Yongjiang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Day Ward, and.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Pathology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Guan
authors.affiliation: Authors' Affiliations: Departments of Urology.
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.affiliation: Authors' Affiliations: Departments of Urology.
authors.forename: Jian
authors.initials: J
authors.lastname: Kang
authors.affiliation: Authors' Affiliations: Departments of Urology.
authors.forename: Xujun
authors.initials: X
authors.lastname: Sheng
authors.affiliation: Authors' Affiliations: Departments of Urology, junqi_xh@126.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Qi
mesh_terms: D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D056744:Cyclin B1 / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D000072100:Jagged-1 Protein; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D064129:Prostatic Neoplasms, Castration-Resistant / Q000235:genetics / Q000378:metabolism / Q000601:surgery; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D016019:Survival Analysis; D014162:Transfection
chemical_list: C410798:AR protein, human; C534699:CCNB1 protein, human; D002135:Calcium-Binding Proteins; D056744:Cyclin B1; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D011944:Receptors, Androgen; D000072099:Serrate-Jagged Proteins; D051057:Proto-Oncogene Proteins c-akt