Estrogen Receptor Inhibits c-Jun-dependent Stress-induced Cell Death by Binding and Modifying c-Jun Activity in Human Breast Cancer Cells
| Autor: | Richard M. Schultz, Rocky Pramanik, Guan Chen, Jiahuai Han, Stanley Borowicz, Xiaomei Qi |
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| Rok vydání: | 2004 |
| Předmět: |
Programmed cell death
DNA Complementary Time Factors Transcription Genetic Proto-Oncogene Proteins c-jun Immunoblotting Mice Nude Estrogen receptor Breast Neoplasms Cell Separation MAP Kinase Kinase 6 Biology Transfection Models Biological Biochemistry Mice Cell Line Tumor Animals Humans Phosphorylation Luciferases Molecular Biology Transcription factor Genes Dominant Cell Nucleus Cell Death Models Genetic c-jun Cell Biology Flow Cytometry Precipitin Tests Receptors Estrogen Apoptosis Calcium-Calmodulin-Dependent Protein Kinases Cancer cell Cancer research Female Signal transduction Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 279:6769-6777 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m311492200 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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