EMAIL THIS PAGE TO A FRIEND

Oncotarget

Silencing of PMEPA1 accelerates the growth of prostate cancer cells through AR, NEDD4 and PTEN.


PMID 25883222

Abstract

Androgen Receptor (AR) is the male hormone receptor and a nuclear transcription factor which plays a central role in the growth of normal and malignant prostate gland. Our earlier studies defined a mechanistic model for male hormone dependent regulation of AR protein levels in prostate cancer (CaP) cells through a negative feed-back loop between AR and PMEPA1, an androgen induced NEDD4 E3 ubiquitin ligase binding protein. This report focuses on the impact of PMEPA1 silencing on CaP biology. PMEPA1 knockdown accelerated the growth of CaP tumor cells in athymic nude mice. In cell culture models knockdown of PMEPA1 resulted in resistance to AR inhibitors enzalutamide and bicalutamide. While, AR protein down regulation by NEDD4 was PMEPA1 dependent, we also noted a PMEPA1 independent downregulation of PTEN by NEDD4. In a subset of human CaP, decreased PMEPA1 mRNA expression significantly correlated with increased levels of AR transcription target PSA, as a surrogate for elevated AR. This study highlights that silencing of PMEPA1 accelerates the growth of CaP cells through AR, NEDD4 and PTEN. Thus, the therapeutic restoration of PMEPA1 represents a promising complementary strategy correcting for AR and PTEN defects in CaP. Statement of significance: Here we define that silencing of PMEPA1 facilitates the growth of CaP cells and modulates AR through NEDD4 and PTEN. The restoration of PMEPA1 represents a promising complementary therapeutic strategy correcting for AR and PTEN defects.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

07-049
Anti-Nedd4 Antibody, WW2 domain, 200 µL, Detect Nedd4 using this Anti-Nedd4 Antibody, WW2 domain validated for use in IH & WB.
SAB4500944
Anti-AKR1B1, C-Terminal antibody produced in rabbit, affinity isolated antibody
SAB1300902
Anti-APS (center) antibody produced in rabbit, saturated ammonium sulfate (SAS) precipitated, buffered aqueous solution
SAB1405474
Anti-KLK3 antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
HPA000764
Anti-KLK3 antibody produced in rabbit, Ab1, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB1410703
Anti-KLK3 antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
SAB4501649
Anti-KLKB1 (heavy chain, Cleaved-Arg390) antibody produced in rabbit, affinity isolated antibody
HPA005634
Anti-KLKB1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
AV45678
Anti-KLKB1 antibody produced in rabbit, IgG fraction of antiserum
SAB2106715
Anti-KLKB1 antibody produced in rabbit, affinity isolated antibody
SAB2101562
Anti-NEDD4 antibody produced in rabbit, affinity isolated antibody
HPA039883
Anti-NEDD4 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB1307231
ANTI-NEDD4(C-TERMINAL) antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
SAB4501531
Anti-Prostate-specific Antigen antibody produced in rabbit, affinity isolated antibody
SAB1303590
ANTI-PSA (C-TERM) antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
SAB4502473
Anti-PTEN, C-Terminal antibody produced in rabbit, affinity isolated antibody
SAB4502474
Anti-PTEN, C-Terminal antibody produced in rabbit, affinity isolated antibody
SAB4502475
Anti-PTEN, C-Terminal antibody produced in rabbit, affinity isolated antibody
SAB4502476
Anti-PTEN, C-Terminal antibody produced in rabbit, affinity isolated antibody
EHU158351 MISSION® esiRNA, esiRNA human PMEPA1 (esiRNA1)
SHC002V
MISSION® pLKO.1-puro Non-Mammalian shRNA Control Transduction Particles, Targets no known mammalian genes
SHCLNV MISSION® shRNA, Lentiviral Particles
WH0000354M2 Monoclonal Anti-KLK3 antibody produced in mouse, clone 1B1, purified immunoglobulin, buffered aqueous solution
SAB5300268
Monoclonal Anti-KLK3 antibody produced in mouse, clone 5A11E9, ascites fluid
WH0056937M1
Monoclonal Anti-TMEPAI antibody produced in mouse, clone 2A12, purified immunoglobulin, buffered aqueous solution
P0044 Phosphatase Inhibitor Cocktail 3, DMSO solution
R0908
R1881, ≥98% (HPLC)
C19H24O2