• Home
  • Search Results
  • PP2A inhibition determines poor outcome and doxorubicin resistance in early breast cancer and its activation shows promising therapeutic effects.

PP2A inhibition determines poor outcome and doxorubicin resistance in early breast cancer and its activation shows promising therapeutic effects.

Oncotarget (2015-03-03)
Raúl Rincón, Ion Cristóbal, Sandra Zazo, Oriol Arpí, Silvia Menéndez, Rebeca Manso, Ana Lluch, Pilar Eroles, Ana Rovira, Joan Albanell, Jesús García-Foncillas, Juan Madoz-Gúrpide, Federico Rojo
ABSTRACT

The protein phosphatase 2A (PP2A) is a key tumor suppressor which has emerged as a novel molecular target in some human cancers. Here, we show that PP2A inhibition is a common event in breast cancer and identified PP2A phosphorylation and deregulation SET and CIP2A as molecular contributing mechanisms to inactivate PP2A. Interestingly, restoration of PP2A activity after FTY720 treatment reduced cell growth, induced apoptosis and decreased AKT and ERK activation. Moreover, FTY720 led to PP2A activation then enhancing doxorubicin-induced antitumor effects both in vitro and in vivo. PP2A inhibition (CPscore: PP2A phosphorylation and/or CIP2A overexpression) was detected in 27% of cases (62/230), and associated with grade (p = 0.017), relapse (p < 0.001), negative estrogen (p < 0.001) and progesterone receptor expression (p < 0.001), HER2-positive tumors (p = 0.049), Ki-67 expression (p < 0.001), and higher AKT (p < 0.001) and ERK (p < 0.001) phosphorylation. Moreover, PP2A inhibition determined shorter overall (p = 0.006) and event-free survival (p = 0.003), and multivariate analysis confirmed its independent prognostic impact. Altogether, our results indicate that PP2A is frequently inactivated in breast cancer and determines worse outcome, and its restoration using PP2A activators represents an alternative therapeutic strategy in this disease.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
L-Glutamine, meets USP testing specifications, suitable for cell culture, 99.0-101.0%, from non-animal source
SAFC
L-Glutamine
Sigma-Aldrich
Trimesic acid, 95%
Sigma-Aldrich
L-Glutamine, ReagentPlus®, ≥99% (HPLC)
Sigma-Aldrich
Trimethylaluminum, 97%
Sigma-Aldrich
Trimethylaluminum solution, 2.0 M in toluene
Sigma-Aldrich
L-Glutamine, BioUltra, ≥99.5% (NT)
Sigma-Aldrich
Trimethylaluminum, packaged for use in deposition systems
Sigma-Aldrich
Trimethylaluminum solution, 2.0 M in hexanes
Sigma-Aldrich
L-Glutamine, γ-irradiated, BioXtra, suitable for cell culture
Supelco
L-Glutamine, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Trimethylaluminum solution, 2.0 M in heptane
Sigma-Aldrich
L-Glutamine
Supelco
L-Glutamine, certified reference material, TraceCERT®

Social Media

LinkedIn icon
Twitter icon
Facebook Icon
Instagram Icon

MilliporeSigma

Research. Development. Production.

We are a leading supplier to the global Life Science industry with solutions and services for research, biotechnology development and production, and pharmaceutical drug therapy development and production.

© 2021 Merck KGaA, Darmstadt, Germany and/or its affiliates. All Rights Reserved.

Reproduction of any materials from the site is strictly forbidden without permission.