Loading...
Please wait, while we are loading the content...
Similar Documents
Epidermal growth factor receptor dependence of radiation-induced transcription factor activation in human breast carcinoma cells.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Amorino, George P. Hamilton, Virginia M. Valerie, Kristoffer Dent, Paul Lammering, Guido M. Schmidt-Ullrich, Rupert K. A. |
| Copyright Year | 2002 |
| Abstract | Ionizing radiation (1-5 Gy) activates the epidermal growth factor receptor (EGFR), a major effector of the p42/44 mitogen-activated protein kinase (MAPK) pathway. MAPK and its downstream effector, p90 ribosomal S6 kinase (p90RSK), phosphorylate transcription factors involved in cell proliferation. To establish the role of the EGFR/MAPK pathway in radiation-induced transcription factor activation, MDA-MB-231 human breast carcinoma cells were examined using specific inhibitors of signaling pathways. Gel-shift analysis revealed three different profile groups: 1) transcription factors that responded to both radiation (2 Gy) and epidermal growth factor (EGF) (CREB, Egr, Ets, and Stat3); 2) factors that responded to radiation, but not EGF (C/EBP and Stat1); and 3) those that did not respond significantly to either radiation or EGF (AP-1 and Myc). Within groups 1 and 2, a two- to fivefold maximum stimulation of binding activity was observed at 30-60 min after irradiation. Interestingly, only transcription factors that responded to EGF had radiation responses significantly inhibited by the EGFR tyrosine kinase inhibitor, AG1478; these responses were also abrogated by farnesyltransferase inhibitor (FTI) or PD98059, inhibitors of Ras and MEK1/2, respectively. Moreover, radiation-induced increases in CREB and p90RSK phosphorylation and activation of Stat3 and Egr-1 reporter constructs by radiation were all abolished by AG1478. These data demonstrate a distinct radiation response profile at the transcriptional level that is dependent on enhanced EGFR/Ras/MAPK signaling. |
| Starting Page | 1 |
| Ending Page | 4 |
| Page Count | 4 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.molbiolcell.org/content/13/7/2233.full.pdf |
| Alternate Webpage(s) | http://www.molbiolcell.org/content/early/2002/04/24/mbc.01-12-0572.full.pdf |
| PubMed reference number | 12134064v1 |
| Volume Number | 13 |
| Issue Number | 7 |
| Journal | Molecular biology of the cell |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | 3,4-Methylenedioxyamphetamine Breast Carcinoma CHOP-C/EBP complex Cell Proliferation Dependence EGFR protein, human Growth Factor Receptors Ionizing radiation MAP Kinase Kinase 4 Mitogen-Activated Protein Kinases Mitogens PD 98059 Protein Tyrosine Kinase Protein-tyrosine kinase inhibitor Ribosomal Protein S6 Kinase Ribosomal Protein S6 Kinases, 90-kDa Stat3 protein TRANSCRIPTION FACTOR Transcription, Genetic tyrphostin AG 1478 |
| Content Type | Text |
| Resource Type | Article |
