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Originally published In Press as doi:10.1074/jbc.M005220200 on September 12, 2000

J. Biol. Chem., Vol. 275, Issue 49, 38524-38531, December 8, 2000
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EGR1 Target Genes in Prostate Carcinoma Cells Identified by Microarray Analysis*

John SvarenDagger §, Torsten EhrigDagger , Sarki A. AbdulkadirDagger , Markus U. Ehrengruber||**, Mark A. WatsonDagger , and Jeffrey MilbrandtDagger Dagger Dagger

From the Dagger  Departments of Pathology and Internal Medicine, Division of Laboratory Medicine, Washington University School of Medicine, St. Louis, Missouri 63110 and the || Brain Research Institute, University of Zurich, Zurich CH-8057, Switzerland

The EGR1 transactivator is overexpressed in prostate cancer, and its expression pattern suggests that EGR1 could potentially regulate a number of steps involved in initiation and progression of prostate cancer, such as mitogenesis, invasiveness, angiogenesis, and metastasis. To identify potential EGR1 target genes in an unbiased manner, we have utilized adenovirus-mediated expression of EGR1 in a prostate cancer cell line to identify specific genes that are induced by EGR1. Using oligonucleotide arrays, a number of EGR1-regulated genes were identified and their regulation was confirmed by quantitative reverse transcription-polymerase chain reaction analysis. One of the largest gene classes identified in this screen includes several neuroendocrine-associated genes (neuron-specific enolase, neurogranin), suggesting that EGR1 overexpression may contribute to the neuroendocrine differentiation that often accompanies prostate cancer progression. This screen also identified several growth factors such as insulin-like growth factor-II, platelet-derived growth factor-A, and transforming growth factor-beta 1, which have previously been implicated in enhancing tumor progression. The insulin-like growth factor-II gene lies within the 11p15.5 chromosomal locus, which contains a number of other imprinted genes, and EGR1 expression was found to induce at least two other genes in this locus (IPL, p57KIP2). Based on our results, coupling adenoviral overexpression with microarray and quantitative reverse transcription-polymerase chain reaction analyses could be a versatile strategy for identifying target genes of transactivators.

* This work was supported in part by National Institutes of Health Grant 5 P01 CA49712-08 and grants from the Association for the Cure of Cancer of the Prostate (CaP CURE) and from the Monsanto Corp.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Present address: Dept. of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.

Supported by National Institutes of Health Training Grant 5 T32 CA 09547-13.

** Supported by Swiss National Science Foundation Grant 31-57/125.99).

Dagger Dagger To whom correspondence should be addressed: Depts. of Pathology and Internal Medicine, Div. of Laboratory Medicine, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110. Tel.: 314-362-4650; Fax: 314-362-8756; E-mail: jeff@pathbox.wustl.edu.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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