One of the most interesting recent developments in the nuclear receptor field has been the identification of natural and synthetic agonists of the peroxisome proliferator-activated receptor (PPAR) family, coupled with a growing recognition that the γ isoform (PPARγ) affects pathways important in a variety of human diseases. Here we show that the activation of PPARγ through the 15-deoxy-Δ-12,14-prostaglandin J2 (PG-J2) ligand causes a dramatic inhibition of ErbB-2 and ErbB-3 tyrosine phosphorylation caused by neuregulin 1 (NRG1) and neuregulin 2 (NRG2) in MCF-7 cells. This effect is accompanied by a very efficient blocking of ErbBs effects upon proliferation, differentiation and cell death in these cells. Preincubation of MCF-7 cells with PG-J2 before addition of NRG1 and NRG2 had a dramatic growth-suppressive effect accompanied by accumulation of cells in the G0/G1 compartment of the cell cycle, and a marked increase in apoptosis. NRG1 and NRG2 induce G1 progression, which was associated with stimulation of the phosphatidylinositol-3 kinase (PI 3-K) pathway, whereas survival was dependent on ERK1/ERK2 activation. Both pathways were inhibited by PG-J2. Furthermore, PG-J2 can abolish the NRG1 and NRG2-induced increase in anchorage-independent growth of these cells. PG-J2 also blocks phosphorylation of other receptor tyrosine kinases, such as IGF-IR, in MCF-7 cells, and suppress proliferation of other breast cancer cell lines. In summary, our data show a specific inhibitory action of PG-J2 on the activity of the ErbB receptors in breast cancer cells.
The peroxisome proliferator-activated receptor γ is an inhibitor of ErbBs activity in human breast cancer cells
Miguel Pignatelli, Marta Cortés-Canteli, Cary Lai, Angel Santos, Ana Perez-Castillo; The peroxisome proliferator-activated receptor γ is an inhibitor of ErbBs activity in human breast cancer cells. J Cell Sci 15 November 2001; 114 (22): 4117–4126. doi: https://doi.org/10.1242/jcs.114.22.4117
Download citation file:
Sign in
Client Account
Sign in via your institution
Sign in via ShibbolethAdvertisement
Cited by
Interviews with Biologists @ 100 conference speakers

Explore our interviews with keynote speakers from the Biologists @ 100 conference, hosted to celebrate our publisher’s 100th anniversary, where we discuss climate change and biodiversity with Hans-Otto Pörtner and Jane Francis, health and disease with Charles Swanton and emerging technologies with Manu Prakash and Jennifer Lippincott-Schwartz.
Introducing our new Associate Editors

In this Editorial, JCS Editor-in-Chief Michael Way welcomes five new Associate Editors to the JCS team. These Associate Editors will expand our support for the wider cell biology community and handle articles in immune cell biology, proteostasis, imaging and image analysis, plant cell biology, and stem cell biology and modelling.
The spatial choreography of mRNA biosynthesis

In their Review, André Ventura-Gomes and Maria Carmo-Fonseca detail the latest research progress and technological advancements that are helping to unlock how nuclear organisation underpins control of gene transcription and pre-mRNA splicing.
JCS-FocalPlane Training Grants

Early-career researchers - working in an area covered by JCS - who would like to attend a microscopy training course, please apply. Deadline dates for 2025 applications: 6 June 2025 (decision by week commencing 28 July 2025) and 5 September 2025 (decision by week commencing 20 October 2025).
The emerging roles of the endoplasmic reticulum in mechanosensing and mechanotransduction

In their Review, Jonathan Townson and Cinzia Progida highlight recently emerging evidence for a role of the endoplasmic reticulum in enabling a cell to sense and respond to changes in the extracellular mechanical environment.