Skip to Content
Merck
  • Silencing of PMEPA1 accelerates the growth of prostate cancer cells through AR, NEDD4 and PTEN.

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

Oncotarget (2015-04-18)
Hua Li, Ahmed A Mohamed, Shashwat Sharad, Elizabeth Umeda, Yingjie Song, Denise Young, Gyorgy Petrovics, David G McLeod, Isabell A Sesterhenn, Taduru Sreenath, Albert Dobi, Shiv Srivastava
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Trypan Blue, Dye content 60 %, ā‰„80% (HPLC)
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Trypan Blue, powder, BioReagent, suitable for cell culture
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Phosphatase Inhibitor Cocktail 3, DMSO solution
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
MISSIONĀ® shRNA, Lentiviral Particles
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Propidium iodide, ā‰„94.0% (HPLC)
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Methanol, NMR reference standard
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Anti-Nedd4, UpstateĀ®, from rabbit
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Propidium iodide solution
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Trypan Blue solution, 0.4%, liquid, sterile-filtered, suitable for cell culture
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
MISSIONĀ® esiRNA, targeting human PMEPA1
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
MISSIONĀ® pLKO.1-puro Non-Mammalian shRNA Control Transduction Particles, Targets no known mammalian genes
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
R1881, ā‰„98% (HPLC)
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Methanol-12C, 99.95 atom % 12C
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Methanol solution, (Methanol:Dimethyl sulfoxide 1:1 (v/v))
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Methanol solution, NMR reference standard, 4% in methanol-d4 (99.8 atom % D), NMR tube size 3 mm Ɨ 8 in.
SKU
Pack Size
Availability
Price
Quantity