Egr1 promotes growth and survival of prostate cancer cells. Identification of novel Egr1 target genes.

Abstract	In the majority of aggressive tumorigenic prostate cancer cells, the transcription factor Egr1 is overexpressed. We provide new insights of Egr1 involvement in proliferation and survival of TRAMP C2 prostate cancer cells by the identification of several new target genes controlling growth, cell cycle progression, and apoptosis such as cyclin D2, P19ink4d, and Fas. Egr1 regulation of these genes, identified by Affymetrix microarray, was confirmed by real-time PCR, immunoblot, and chromatin immunoprecipitation assays. Furthermore we also showed that Egr1 is responsible for cyclin D2 overexpression in tumorigenic DU145 human prostate cells. The regulation of these genes by Egr1 was demonstrated using Egr1 antisense oligonucleotides that further implicated Egr1 in resistance to apoptotic signals. One mechanism was illustrated by the ability of Egr1 to inhibit CD95 (Fas/Apo) expression, leading to insensitivity to FasL. The results provide a mechanistic basis for the oncogenic role of Egr1 in TRAMP C2 prostate cancer cells.
Authors	Thierry Virolle, Anja Krones-Herzig, Veronique Baron, Giorgia De Gregorio, Eileen D Adamson, Dan Mercola
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 278 Issue 14 Pg. 11802-10 (Apr 04 2003) ISSN: 0021-9258 [Print] United States
PMID	12556466 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
Chemical References	Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Ccnd2 protein, mouse Cdkn2d protein, mouse Cell Cycle Proteins Cyclin D2 Cyclin-Dependent Kinase Inhibitor p16 Cyclin-Dependent Kinase Inhibitor p19 Cyclins DNA-Binding Proteins Early Growth Response Protein 1 Egr1 protein, mouse FASLG protein, human Fas Ligand Protein Fasl protein, mouse Immediate-Early Proteins Mad protein, mouse Membrane Glycoproteins Oligodeoxyribonucleotides, Antisense Repressor Proteins Transcription Factors fas Receptor
Topics	Animals Apoptosis (genetics, physiology) Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Cell Cycle Proteins Cell Division (physiology) Cell Survival (physiology) Cyclin D2 Cyclin-Dependent Kinase Inhibitor p16 (genetics) Cyclin-Dependent Kinase Inhibitor p19 Cyclins (genetics) DNA-Binding Proteins (genetics, physiology) Early Growth Response Protein 1 Fas Ligand Protein Gene Expression Regulation, Neoplastic Immediate-Early Proteins Male Membrane Glycoproteins (metabolism) Mice Oligodeoxyribonucleotides, Antisense (pharmacology) Prostatic Neoplasms (genetics, pathology) Repressor Proteins Transcription Factors (genetics, physiology) Transcriptional Activation (physiology) Tumor Cells, Cultured fas Receptor (genetics, metabolism)

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