Related Experiment Video

Updated: May 20, 2026

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
09:07

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay

Published on: December 19, 2018

Inhibition of p38-MAPK alters SRC coactivation and estrogen receptor phosphorylation

James W Antoon1, Melyssa R Bratton, Lori M Guillot

  • 1Department Medicine, Section of Hematology and Medical Oncology, Tulane University School of Medicine, New Orleans, LA, USA.

Cancer Biology & Therapy
|July 25, 2012
PubMed

Insights

Targeting the p38 mitogen activated protein kinase (MAPK) pathway with RWJ67657 inhibits estrogen receptor-positive breast cancer cell survival. This novel p38 inhibitor shows therapeutic potential for ER(+) breast cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • The p38 mitogen activated protein kinase (MAPK) pathway promotes cell survival and endocrine therapy resistance in estrogen receptor-positive (ER(+)) breast cancer.
  • Targeting the p38 MAPK pathway presents a potential therapeutic strategy for ER(+) breast cancer.

Purpose of the Study:

  • To investigate the efficacy of the novel p38 inhibitor RWJ67657 in ER(+) breast cancer cells.
  • To elucidate the mechanisms by which p38 MAPK influences ERα activity and breast cancer cell proliferation.

Main Methods:

  • Utilized the p38 inhibitor RWJ67657 in the ER(+) breast cancer cell line MCF-7.
  • Assessed inhibition of p38α phosphorylation and downstream targets (hsp27, MAPAPK).
  • Evaluated effects on clonogenic survival, ERα transcriptional activation, and coactivator activity (SRC-1, -2, -3).

Main Results:

  • RWJ67657 inhibited basal and estrogen-stimulated p38α phosphorylation, decreasing downstream target activation.
  • p38α inhibition by RWJ67657 blocked MCF-7 cell clonogenic survival with minimal impact on non-cancerous cells.
  • RWJ67657 inhibited ERα transcriptional activation by targeting both AF-1 and AF-2 domains and decreased ERα coactivator activity.

Conclusions:

  • The p38 MAPK pathway plays a significant role in ER(+) breast cancer cell survival and proliferation.
  • RWJ67657 effectively inhibits p38α signaling, leading to decreased ERα activity and breast cancer cell survival.
  • Targeting the p38 MAPK pathway with RWJ67657 demonstrates therapeutic potential for ER(+) breast cancer treatment.

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