Early growth response 3 (Egr3) is highly over-expressed in non-relapsing prostate cancer but not in relapsing prostate cancer.

Abstract

Members of the early growth response (EGR) family of transcription factors play diverse functions in response to many cellular stimuli, including growth, stress, and inflammation. Egr3 has gone relatively unstudied, but here through use of the SPECS (Strategic Partners for the Evaluation of Predictive Signatures of Prostate Cancer) Affymetrix whole genome gene expression database we report that Egr3 mRNA is significantly over-expressed in prostate cancer compared to normal prostate tissue (5-fold). The Human Protein Atlas (http://www.proteinatlas.org), a database of tissue microarrays labeled with antibodies against over 11,000 human proteins, was utilized to quantify Egr3 protein expression in normal prostate and prostate cancer patients. In agreement with the SPECS data, we found that Egr3 protein is significantly increased in prostate cancer. The SPECS database has the benefit of extensive clinical follow up for the prostate cancer patients. Analysis of Egr3 mRNA expression in relation to the relapse status reveals that Egr3 mRNA expression is increased in tumor cells of non-relapsed samples (n = 63) compared to normal prostate cells, but is significantly lower in relapsed samples (n = 38) compared to non-relapse. The observations were confirmed using an independent data set. A list of genes correlating with this unique expression pattern was determined. These Egr3-correlated genes were enriched with Egr binding sites in their promoters. The gene list contains inflammatory genes such as IL-6, IL-8, IL1β and COX-2, which have extensive connections to prostate cancer.