These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: The activity of the androgen receptor variant AR-V7 is regulated by FOXO1 in a PTEN-PI3K-AKT-dependent way.
    Author: Mediwala SN, Sun H, Szafran AT, Hartig SM, Sonpavde G, Hayes TG, Thiagarajan P, Mancini MA, Marcelli M.
    Journal: Prostate; 2013 Feb 15; 73(3):267-77. PubMed ID: 22821817.
    Abstract:
    BACKGROUND: The androgen receptor (AR) AR-V7 splice isoform is a constitutively active outlaw transcription factor. Transition of prostate cancer (PC) to the castration-resistant phenotype correlates with AR-V7 accumulation, suggesting that PC progression in patients refractory to conventional therapy is due to the activity of this AR isoform. The mechanism of AR-V7 constitutive activation is not known. METHODS: We analyzed potential signaling pathways associated with AR-V7 constitutive activation in PTEN (-) PC-3 and LNCaP cells. We used transient and stable transfection, reporter gene assay, RNAi technology together with a number of kinase inhibitors to determine if AR-V7 activation is linked to a kinase-dependent signaling pathway. RESULTS: In these cell lines, AR-V7 transcriptional activity was inhibited by LY294002, Wortmanin, and AKT inhibitor II. Analysis of the contributing mechanisms demonstrated the involvement of the Phosphatidylinositol 3-kinase (PI3K)-AKT-FOXO1 signaling pathway, and a significant reduction of AR-V7 constitutive activity under conditions of PTEN reactivation. CONCLUSIONS: Our study identifies a pathway regulating AR-V7 constitutive activity and potential therapeutic targets for the treatment of castration-resistant PC.
    [Abstract] [Full Text] [Related] [New Search]