Androgen receptor promotes the oncogenic function of overexpressed Jagged1 in prostate cancer by enhancing cyclin B1 expression via Akt phosphorylation.

UNLABELLED: 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. IMPLICATIONS: This study could benefit our clinical treatments for patients with prostate cancer with overexpressed Jagged1 by targeting AR and Akt. ©2014 American Association for Cancer Research.