Accession Number:

AD1047585

Title:

Targeting a Novel Androgen Receptor-Repressed Pathway in Prostate Cancer Therapy

Descriptive Note:

Technical Report,01 Sep 2016,31 Aug 2017

Corporate Author:

University of Pittsburgh Pittsburgh United States

Personal Author(s):

Report Date:

2017-09-01

Pagination or Media Count:

45.0

Abstract:

The primary goal of this study is to investigate the potential roles of protein kinase D PKD in mediating therapeutic resistance to ADT and to investigate the impact of PKD small molecule inhibitor SMI-based combination therapies to curtail ADT-induced therapy resistance. During the past funding cycle, we examined the cross-regulation of PKD1 by androgen signaling in prostate cancer cells. Our data has identified PKD1 as a novel androgen-repressed gene at transcriptional level. Kinetic analysis indicated that the repression of PKD1 by androgen required the induction of a repressor protein, and AR was required for the suppression of PKD1 by androgen. Downstream of AR, we identified fibroblast growth factor receptor substrate 2 FRS2 and its downstream MEKERK pathway as the mediators of androgen-induced PKD1 repression. Our study indicates that PKD1 is a novel androgen suppressed gene and can be downregulated by androgen through a novel ARFRS2MEKERK pathway.The upregulation of the prosurvival PKD1 by antiandrogens may contribute to therapeutic resistance in prostate cancer treatment.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE