Induction of Egr-1 expression by the retinoid AHPN in human lung carcinoma cells is dependent on activated ERK1/2
| Autor: | Hiroshi Adachi, Marcia I. Dawson, Anton M. Jetten, Morito Sakaue |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Transcriptional Activation
Programmed cell death Lung Neoplasms Nerve growth factor IB medicine.drug_class p38 mitogen-activated protein kinases Antineoplastic Agents Apoptosis Models Biological p38 Mitogen-Activated Protein Kinases Immediate-Early Proteins Retinoids Gene expression Tumor Cells Cultured medicine Humans RNA Neoplasm Retinoid Molecular Biology Early Growth Response Protein 1 Oligonucleotide Array Sequence Analysis Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Chemistry Cell growth Carcinoma Cell Biology Cell biology DNA-Binding Proteins Enzyme Activation Proto-Oncogene Proteins c-bcl-2 Mitogen-Activated Protein Kinases Signal transduction Cell Division Transcription Factors |
| Zdroj: | Cell Death & Differentiation. 8:411-424 |
| ISSN: | 1476-5403 1350-9047 |
| DOI: | 10.1038/sj.cdd.4400818 |
| Popis: | The novel retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (AHPN/CD437) inhibits cell proliferation and is a very effective inducer of apoptosis in a variety of carcinoma cell lines. In order to obtain greater insight into the mechanism of AHPN-induced growth arrest and apoptosis, we began to examine AHPN-induced changes in gene expression by cDNA array screening using human lung carcinoma H460 cells. This analysis identified several AHPN-inducible genes, including the immediate-early genes Egr-1 and Nur77. AHPN was able to increase Egr-1 and Nur77 mRNA expression and protein in a variety of carcinoma cell lines. This induction appeared to be regulated at the transcriptional level and was specific for AHPN since an RAR- and an RXR-selective retinoid were inactive. These results suggest that the induction of Egr-1 and Nur77 by AHPN is independent of nuclear retinoid receptors and involves a novel mechanism. Overexpression of Bcl-2, which inhibits AHPN-induced apoptosis but not growth arrest in human T cell lymphoma Molt-4 cells, did not block the induction of immediate-early gene expression. Treatment of H460 cells with AHPN induced activation of the p38 MAP-kinase but not the ERK1/2 signaling pathway. However, inhibition of the ERK1/2 signaling pathway by PD98059 blocked the induction of Egr-1 and Nur77 mRNA while the p38 MAPK inhibitor PD169316 had little effect. Expression of a dominant-negative ERK1 completely abolished the increase in Egr-1 mRNA. Treatment with MAPK inhibitors or expression of dnERK1 reduced but did not block AHPN-induced apoptosis. Our results suggest that the induction of Egr-1 in H460 by AHPN requires active ERK1/2 and is independent of p38 activation. Egr-1, in cooperation with several other growth-suppressor proteins, is likely involved in AHPN-induced inhibition of cell growth and cell death. Cell Death and Differentiation (2001) 8, 411–424 |
| Databáze: | OpenAIRE |
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