Faculty Collaboration Database

Estrogen receptor inhibits c-Jun-dependent stress-induced cell death by binding and modifying c-Jun activity in human breast cancer cells. J Biol Chem 2004 Feb 20;279(8):6769-77

Date

11/26/2003

Pubmed ID

14638681

DOI

10.1074/jbc.M311492200

Scopus ID

2-s2.0-1342325421 (requires institutional sign-in at Scopus site)   29 Citations

Abstract

c-Jun, a major component of the AP-1 transcription factor, is either pro- or anti-apoptotic with cellular determinants unknown. Nuclear estrogen receptor (ER), on the other hand, regulates gene expression through both estrogen response elements and AP-1. Here we show that stress stimulates c-Jun phosphorylation and AP-1 activity in both ER+ and ER- human breast cancer cells and only induces cell death in ER- cells, indicating a determinant role of ER in c-Jun/AP-1 activity. The inhibitory effect of ER in stress-induced cell death is confirmed by ER transfection into ER- cells. Furthermore, inhibition of c-Jun activation by a dominant negative c-Jun blocks AP-1 activity in ER+ cells and attenuates stress-induced cell death but not AP-1 activity in ER- cells, suggesting that the c-Jun/AP-1 activity has distinct properties depending on ER status. ER was shown to inhibit stress-induced cell death through its physical interaction with c-Jun. This is because ER binds c-Jun in breast cancer cells, stress treatment further increases the ER-bound phosphorylated c-Jun, and the c-Jun binding-deficient ER mutant fails to protect stress-induced cell death. Together, our studies reveal a novel function of ER in stress response by modification of c-Jun activity.

Author List

Qi X, Borowicz S, Pramanik R, Schultz RM, Han J, Chen G

Authors

Guan Chen MD, PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Xiao-Mei Qi MD Associate Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Breast Neoplasms
Calcium-Calmodulin-Dependent Protein Kinases
Cell Death
Cell Line, Tumor
Cell Nucleus
Cell Separation
DNA, Complementary
Female
Flow Cytometry
Genes, Dominant
Humans
Immunoblotting
Luciferases
MAP Kinase Kinase 6
Mice
Mice, Nude
Models, Biological
Models, Genetic
Phosphorylation
Precipitin Tests
Protein Binding
Proto-Oncogene Proteins c-jun
Receptors, Estrogen
Time Factors
Transcription, Genetic
Transfection